Skip to main content
SpringerLink
Log in

Resistance to Y-90 Ibritumomab Tiuxetan Therapy

  • Chapter
  • First Online:
Resistance to Ibritumomab in Lymphoma

Part of the book series: Resistance to Targeted Anti-Cancer Therapeutics ((RTACT,volume 18))

  • 250 Accesses

Abstract

Y-90 ibritumomab tiuxetan is the first radioimmunotherapy (RIT) agent for patients with relapsed or refractory low-grade CD20-positive B-cell non-Hodgkin’s lymphoma. Although accumulated data demonstrate its excellent therapeutic efficiency, there are a certain number of patients that experience disease exacerbation during the post-RIT observation periods. Up to now, advanced disease, bulky mass, poor performance status, a history of frequent chemotherapies before RIT, etc. have been proposed as predictive factors for unfavorable prognosis after RIT. In this chapter, we focus on the bulky disease, the downregulation of the CD20 molecule, the NF-𝜅B activation, and the impaired host immune status as factors presumably related to resistance to Y-90 ibritumomab tiuxetan therapy. We also discuss the mechanisms of the resistance and rational therapeutic approaches. We further illustrate the immunological circumstances in tumor-bearing patients and comment on the immune checkpoint blockade therapy.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 84.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 109.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 109.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Abbreviations

ABC:

Activated B-like diffuse large B-cell lymphoma

ADCC:

Antibody-dependent cellular cytotoxicity

Ag:

Antigen

APC:

Antigen-presenting cell

ATP:

Adenosine triphosphate

BT:

Bulky tumor

CD:

Cluster of differentiation

CDC:

Complement-dependent cytotoxicity

ODN:

Oligodeoxynucleotides

CR:

Complete response

CRR:

Complete response rate

CRT:

Calreticulin

CTLA-4:

Cytotoxic T-lymphocyte-associated protein-4

DA-EPOCH-R:

Dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab

DAMP:

Damage-associated molecular patterns

DC:

Dendritic cell

DLBCL:

Diffuse large B-cell lymphoma

EBRT:

Extrabeam radiotherapy

EU:

European Union

F(ab′)2:

Fab prime 2

Fab:

Fragment antigen-binding

Fas-L:

Fas-ligand

FcγR:

Fcγ receptor

FIT:

First-line indolent trial

Flt3-L:

Fms-like tyrosine kinase 3 ligand

GCB:

Germinal center B cell

GMCSF:

Granulocyte macrophage colony-stimulating factor

HcAb:

Heavy-chain antibody

HMGB1:

High-mobility group box 1

ICD:

Immunological cell death

IFN:

Interferon

IL:

Interleukin

IPI:

International Prognostic Index

mAb:

Monoclonal antibody

MCL:

Mantle-cell lymphoma

MDSC:

Myeloid-derived suppressor cells

MHC:

Major histocompatibility complex

MRD:

Minimal residual disease

NF-κB:

Nuclear factor-κB

ORR:

Overall response rate

PD-1:

Programmed cell death-1

PD-L1:

Programed cell death ligand 1

PFS:

Progression-free survival

P2RX7:

Purinergic receptor P2X, ligand gated ion channel, 7

R-CHOP:

Rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone

RIT:

Radioimmunotherapy

RN:

Radionuclide

scFv:

Single-chain variable

TCR:

T cell receptor

TGF-β:

Transforming growth factor beta

TLR:

Toll-like receptor

TNFα:

Tumor necrosis factor α

Treg:

Regulatory T cells

TTP:

Time to disease progression

US FDA:

US Food and Drug Administration

Y-90:

Yttrium-90

References

  1. Witzig TE, White CA, Wiseman GA, Gordon LI, Emmanouilides C, Raubitschek A, Janakiraman N, Gutheil J, Schilder RJ, Spies S, Silverman DH, Parker E, Grillo-López AJ. Phase I/II trial of IDEC-Y2B8 radioimmunotherapy for treatment of relapsed or refractory CD20(+) B-cell non-Hodgkin’s lymphoma. J Clin Oncol. 1999;17:3793–803.

    Article  CAS  PubMed  Google Scholar 

  2. Witzig TE, Flinn IW, Gordon LI, Emmanouilides C, Czuczman MS, Saleh MN, Cripe L, Wiseman G, Olejnik T, Multani PS, White CA. Treatment with ibritumomab tiuxetan radioimmunotherapy in patients with rituximab-refractory follicular non-Hodgkin’s lymphoma. J Clin Oncol. 2002;20:3262–9.

    Article  CAS  PubMed  Google Scholar 

  3. Witzig TE, Gordon LI, Cabanillas F, Czuczman MS, Emmanouilides C, Joyce R, Pohlman BL, Bartlett NL, Wiseman GA, Padre N, Grillo-López AJ, Multani P, White CA. Randomized controlled trial of yttrium-90-labeled ibritumomab tiuxetan radioimmunotherapy versus rituximab immunotherapy for patients with relapsed or refractory low-grade, follicular, or transformed B-cell non-Hodgkin’s lymphoma. J Clin Oncol. 2002;20:2453–63.

    Article  CAS  PubMed  Google Scholar 

  4. Tobinai K, Watanabe T, Ogura M, Morishima Y, Hotta T, Ishizawa K, Itoh K, Okamoto S, Taniwaki M, Tsukamoto N, Okumura H, Terauchi T, Nawano S, Matsusako M, Matsuno Y, Nakamura S, Mori S, Ohashi Y, Hayashi M, Endo K. Japanese phase II study of 90Y-ibritumomab tiuxetan in patients with relapsed or refractory indolent B-cell lymphoma. Cancer Sci. 2009;100:158–64.

    Article  CAS  PubMed  Google Scholar 

  5. Uike N, Choi I, Tsuda M, Haji S, Toyoda K, Suehiro Y, Abe Y, Hayashi T, Sawamoto H, Kaneko K, Shimokawa M, Nakagawa M. Factors associated with effects of 90Y-ibritumomab tiuxetan in patients with relapsed or refractory low-grade B cell non-Hodgkin lymphoma: single-institution experience with 94 Japanese patients in rituximab era. Int J Hematol. 2014;100:386–92.

    Article  CAS  PubMed  Google Scholar 

  6. Morschhauser F, Radford J, Van Hoof A, Botto B, Rohatiner AZ, Salles G, Soubeyran P, Tilly H, Bischof-Delaloye A, van Putten WL, Kylstra JW, Hagenbeek A. 90Yttrium-ibritumomab tiuxetan consolidation of first remission in advanced-stage follicular non-Hodgkin lymphoma: updated results after a median follow-up of 7.3 years from the International, Randomized, Phase III First-Line Indolent trial. J Clin Oncol 2013;31:1977–83.

    Article  CAS  PubMed  Google Scholar 

  7. Witzig TE, Molina A, Gordon LI, Emmanouilides C, Schilder RJ, Flinn IW, Darif M, Macklis R, Vo K, Wiseman GA. Long-term responses in patients with recurring or refractory B-cell non-Hodgkin lymphoma treated with yttrium 90 ibritumomab tiuxetan. Cancer. 2007;109:1804–10.

    Article  CAS  PubMed  Google Scholar 

  8. Fisher RI, Kaminski MS, Wahl RL, Knox SJ, Zelenetz AD, Vose JM, Leonard JP, Kroll S, Goldsmith SJ, Coleman M. Tositumomab and iodine-131 tositumomab produces durable complete remissions in a subset of heavily pretreated patients with low-grade and transformed non-Hodgkin’s lymphomas. J Clin Oncol. 2005;23:7565–73.

    Article  CAS  PubMed  Google Scholar 

  9. Emmanouilides C, Witzig TE, Gordon LI, Vo K, Wiseman GA, Flinn IW, Darif M, Schilder RJ, Molina A. Treatment with yttrium 90 ibritumomab tiuxetan at early relapse is safe and effective in patients with previously treated B-cell non-Hodgkin’s lymphoma. Leuk Lymphoma. 2006;47:629–36.

    Article  CAS  PubMed  Google Scholar 

  10. Rajguru S, Kristinsdottir T, Eickhoff J, Peterson C, Meyer CM, Traynor AM, Kahl BS. Yttrium 90-ibritumomab tiuxetan plus rituximab maintenance as initial therapy for patients with high-tumor-burden follicular lymphoma: a Wisconsin Oncology Network study. Clin Adv Hematol Oncol. 2014;12:509–15.

    PubMed  Google Scholar 

  11. Fruchart C, Tilly H, Morschhauser F, Ghesquières H, Bouteloup M, Fermé C, Van Den Neste E, Bordessoule D, Bouabdallah R, Delmer A, Casasnovas RO, Ysebaert L, Ciappuccini R, Briere J, Gisselbrecht C. Upfront consolidation combining yttrium-90 ibritumomab tiuxetan and high-dose therapy with stem cell transplantation in poor-risk patients with diffuse large B cell lymphoma. Biol Blood Marrow Transplant. 2014;20:1905–11.

    Article  CAS  PubMed  Google Scholar 

  12. Wiseman GA, White CA, Sparks RB, Erwin WD, Podoloff DA, Lamonica D, Bartlett NL, Parker JA, Dunn WL, Spies SM, Belanger R, Witzig TE, Leigh BR. Biodistribution and dosimetry results from a phase III prospectively randomized controlled trial of Zevalin radioimmunotherapy for low-grade, follicular, or transformed B-cell non-Hodgkin’s lymphoma. Crit Rev Oncol Hematol. 2001;39:181–94.

    Article  CAS  PubMed  Google Scholar 

  13. Witzig TE, White CA, Wiseman GA, Gordon LI, Emmanouilides C, Raubitschek A, Janakiraman N, Gutheil J, Schilder RJ, Spies S, Silverman DH, Parker E, Grillo-López AJ. Phase I/II trial of IDEC-Y2B8 radioimmunotherapy for treatment of relapsed or refractory CD20(+) B-cell non-Hodgkin’s lymphoma. J Clinical Oncologia. 1999;17:3793–803.

    Article  CAS  Google Scholar 

  14. Samaniego F, Berkova Z, Romaguera JE, Fowler N, Fanale MA, Pro B, Shah JJ, McLaughlin P, Sehgal L, Selvaraj V, Braun FK, Mathur R, Feng L, Neelapu SS, Kwak LW. 90Y-ibritumomab tiuxetan radiotherapy as first-line therapy for early stage low-grade B-cell lymphomas, including bulky disease. Br J Haematol. 2014;167:207–13.

    Article  CAS  PubMed  Google Scholar 

  15. Tamura S, Ikeda T, Kurihara T, Kakuno Y, Nasu H, Nakano Y, Oshima K, Fujimoto T. Bulky pulmonary mucosa-associated lymphoid tissue lymphoma treated with yttrium-90 ibritumomab tiuxetan. Case Rep Hematol. 2013;2013:675187. https://doi.org/10.1155/2013/675187.

    Article  PubMed  PubMed Central  Google Scholar 

  16. Ibatici A, Pica GM, Nati S, Vitolo U, Botto B, Ciochetto C, Petrini M, Galimberti S, Ciabatti E, Orciuolo E, Zinzani PL, Cascavilla N, Guolo F, Fraternali Orcioni G, Carella AM. Safety and efficacy of (90) yttrium-ibritumomab-tiuxetan for untreated follicular lymphoma patients. an Italian cooperative study. Br J Haematol. 2014;164:710–6.

    Article  CAS  PubMed  Google Scholar 

  17. Gokhale AS, Mayadev J, Pohlman B, Macklis RM. Gamma camera scans and pretreatment tumor volumes as predictors of response and progression after Y-90 anti-CD20 radioimmunotherapy. Int J Radiat Oncol Biol Phys. 2005;63:194–201.

    Article  PubMed  Google Scholar 

  18. Jacobs SA, Harrison AM, Swerdlow SH, Foon KA, Avril N, Vidnovic N, Joyce J, DeMonaco N, McCarty KS Jr. Radioisotopic localization of (90)Yttrium-ibritumomab tiuxetan in patients with CD20+ non-Hodgkin’s lymphoma. Mol Imaging Biol. 2009;11:39–45.

    Article  CAS  PubMed  Google Scholar 

  19. Green DJ, Shadman M, Jones JC, Frayo SL, Kenoyer AL, Hylarides MD, Hamlin DK, Wilbur DS, Balkan ER, Lin Y, Miller BW, Frost SH, Gopal AK, Orozco JJ, Gooley TA, Laird KL, Till BG, Bäck T, Sandmaier BM, Pagel JM, Press OW. Astatine-211 conjugated to an anti-CD20 monoclonal antibody eradicates disseminated B-cell lymphoma in a mouse model. Blood. 2015;125:2111–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Morschhauser F, Radford J, Van Hoof A, Vitolo U, Soubeyran P, Tilly H, Huijgens PC, Kolstad A, d’Amore F, Gonzalez Diaz M, Petrini M, Sebban C, Zinzani PL, van Oers MH, van Putten W, Bischof-Delaloye A, Rohatiner A, Salles G, Kuhlmann J, Hagenbeek A. Phase III trial of consolidation therapy with yttrium-90-ibritumomab tiuxetan compared with no additional therapy after first remission in advanced follicular lymphoma. J Clin Oncol. 2008;26:5156–64.

    Article  CAS  PubMed  Google Scholar 

  21. McLaughlin P, Hagemeister FB, Romaguera JE, Sarris AH, Pate O, Younes A, Swan F, Keating M, Cabanillas F. Fludarabine, mitoxantrone, and dexamethasone: an effective new regimen for indolent lymphoma. J Clin Oncol. 1996;14:1262–8.

    Article  CAS  PubMed  Google Scholar 

  22. Zinzani PL, Tani M, Pulsoni A, Gobbi M, Perotti A, De Luca S, Fabbri A, Zaccaria A, Voso MT, Fattori P, Guardigni L, Ronconi S, Cabras MG, Rigacci L, De Renzo A, Marchi E, Stefoni V, Fina M, Pellegrini C, Musuraca G, Derenzini E, Pileri S, Fanti S, Piccaluga PP, Baccarani M. Fludarabine and mitoxantrone followed by yttrium-90 ibritumomab tiuxetan in previously untreated patients with follicular non-Hodgkin lymphoma trial: a phase II non-randomised trial (FLUMIZ). Lancet Oncol. 2008;9:352–8.

    Article  CAS  PubMed  Google Scholar 

  23. Jacobs SA, Swerdlow SH, Kant J, Foon KA, Jankowitz R, Land SR, DeMonaco N, Joyce J, Osborn JL, Evans TL, Schaefer PM, Luong TM. Phase II trial of short-course CHOP-R followed by 90Y-ibritumomab tiuxetan and extended rituximab in previously untreated follicular lymphoma. Clin Cancer Res. 2008;14:7088–94.

    Article  CAS  PubMed  Google Scholar 

  24. Burdick MJ, Neumann D, Pohlman B, Reddy CA, Tendulkar RD, Macklis R. External beam radiotherapy followed by 90Y ibritumomab tiuxetan in relapsed or refractory bulky follicular lymphoma. Int J Radiat Oncol Biol Phys. 2011;79:1124–30.

    Article  CAS  PubMed  Google Scholar 

  25. Beckman RA, Weiner LM, Davis HM. Antibody constructs in cancer therapy: protein engineering strategies to improve exposure in solid tumors. Cancer. 2007;109:170–9.

    Article  CAS  PubMed  Google Scholar 

  26. Jain RK, Stylianopoulos T. Delivering nanomedicine to solid tumors. Nat Rev Clin Oncol. 2010;7:653–64.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Oliveira S, van Dongen GA, Stigter-van Walsum M, Roovers RC, Stam JC, Mali W, van Diest PJ, van Bergen en Henegouwen PM. Rapid visualization of human tumor xenografts through optical imaging with a near-infrared fluorescent anti-epidermal growth factor receptor nanobody. Mol Imaging. 2012;11:33–46.

    Article  CAS  PubMed  Google Scholar 

  28. Hamers-Casterman C, Atarhouch T, Muyldermans S, Robinson G, Hamers C, Songa EB, Bendahman N, Hamers R. Naturally occurring antibodies devoid of light chains. Nature. 1993;363:446–8.

    Article  CAS  PubMed  Google Scholar 

  29. Keyaerts M, Xavier C, Heemskerk J, Devoogdt N, Everaert H, Ackaert C, Vanhoeij M, Duhoux FP, Gevaert T, Simon P, Schallier D, Fontaine C, Vaneycken I, Vanhove C, De Greve J, Lamote J, Caveliers V, Lahoutte T. Phase I Study of 68Ga-HER2-Nanobody for PET/CT Assessment of HER2 Expression in Breast Carcinoma. J Nucl Med. 2016;57:27–33.

    Article  CAS  PubMed  Google Scholar 

  30. Chatalic KL, Veldhoven-Zweistra J, Bolkestein M, Hoeben S, Koning GA, Boerman OC, de Jong M, van Weerden WM. A Novel 111In-labeled anti-prostate-specific membrane antigen nanobody for targeted SPECT/CT imaging of prostate cancer. J Nucl Med. 2015;56:1094–9.

    Article  CAS  PubMed  Google Scholar 

  31. Ding L, Tian C, Feng S, Fida G, Zhang C, Ma Y, Ai G, Achilefu S, Gu Y. Small sized EGFR1 and HER2 specific bifunctional antibody for targeted cancer therapy. Theranostics. 2015;5:378–98.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  32. Kijanka M, Dorresteijn B, Oliveira S, van Bergen en Henegouwen PM. Nanobody-based cancer therapy of solid tumors. Nanomedicine (Lond). 2015;10:161–74.

    Article  CAS  Google Scholar 

  33. D’Huyvetter M, Vincke C, Xavier C, Aerts A, Impens N, Baatout S, De Raeve H, Muyldermans S, Caveliers V, Devoogdt N, Lahoutte T. Targeted radionuclide therapy with A 177Lu-labeled anti-HER2 nanobody. Theranostics. 2014;4:708–20.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  34. Kraeber-Bodéré F, Rousseau C, Bodet-Milin C, Frampas E, Faivre-Chauvet A, Rauscher A, Sharkey RM, Goldenberg DM, Chatal JF, Barbet JA. pretargeting system for tumor PET imaging and radioimmunotherapy. Front Pharmacol. 2015 Mar 31;6:54. https://doi.org/10.3389/fphar.2015.00054.

    Article  PubMed  PubMed Central  Google Scholar 

  35. Axworthy DB, Reno JM, Hylarides MD, Mallett RW, Theodore LJ, Gustavson LM, Su F, Hobson LJ, Beaumier PL, Fritzberg AR. Cure of human carcinoma xenografts by a single dose of pretargeted yttrium-90 with negligible toxicity. Proc Natl Acad Sci U S A. 2000;97:1802–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Pagel JM, Pantelias A, Hedin N, Wilbur S, Saganic L, Lin Y, Axworthy D, Hamlin DK, Wilbur DS, Gopal AK, Press OW. Evaluation of CD20, CD22, and HLA-DR targeting for radioimmunotherapy of B-cell lymphomas. Cancer Res. 2007;67:5921–8.

    Article  CAS  PubMed  Google Scholar 

  37. Sharkey RM, Karacay H, Litwin S, Rossi EA, McBride WJ, Chang CH, Goldenberg DM. Improved therapeutic results by pretargeted radioimmunotherapy of non-Hodgkin’s lymphoma with a new recombinant, trivalent, anti-CD20, bispecific antibody. Cancer Res. 2008;68:5282–90.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Chatal JF, Campion L, Kraeber-Bodéré F, Bardet S, Vuillez JP, Charbonnel B, Rohmer V, Chang CH, Sharkey RM, Goldenberg DM, Barbet J, French Endocrine Tumor Group. Survival improvement in patients with medullary thyroid carcinoma who undergo pretargeted anti-carcinoembryonic-antigen radioimmunotherapy: a collaborative study with the French Endocrine Tumor Group. J Clin Oncol. 2006;24:1705–11.

    Article  CAS  PubMed  Google Scholar 

  39. Salaun PY, Campion L, Bournaud C, Faivre-Chauvet A, Vuillez JP, Taieb D, Ansquer C, Rousseau C, Borson-Chazot F, Bardet S, Oudoux A, Cariou B, Mirallié E, Chang CH, Sharkey RM, Goldenberg DM, Chatal JF, Barbet J, Kraeber-Bodéré F. Phase II trial of anticarcinoembryonic antigen pretargeted radioimmunotherapy in progressive metastatic medullary thyroid carcinoma: biomarker response and survival improvement. J Nucl Med. 2012;53:1185–92.

    Article  CAS  PubMed  Google Scholar 

  40. Deans JP, Li H, Polyak MJ. CD20-mediated apoptosis: signalling through lipid rafts. Immunology. 2002;107:176–82.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Li H, Ayer LM, Lytton J, Deans JP. Store-operated cation entry mediated by CD20 in membrane rafts. J Biol Chem. 2003;278:42427–34.

    Article  CAS  PubMed  Google Scholar 

  42. Brown DA, London E. Structure and function of sphingolipid- and cholesterol-rich membrane rafts. J Biol Chem. 2000;275:17221–4.

    Article  CAS  PubMed  Google Scholar 

  43. Bubien JK, Zhou LJ, Bell PD, Frizzell RA, Tedder TF. Transfection of the CD20 cell surface molecule into ectopic cell types generates a Ca2+ conductance found constitutively in B lymphocytes. J Cell Biol. 1993;121:1121–32.

    Article  CAS  PubMed  Google Scholar 

  44. Johnson NA, Boyle M, Bashashati A, Leach S, Brooks-Wilson A, Sehn LH, Chhanabhai M, Brinkman RR, Connors JM, Weng AP, Gascoyne RD. Diffuse large B-cell lymphoma: reduced CD20 expression is associated with an inferior survival. Blood. 2009;113:3773–80.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Almasri NM, Duque RE, Iturraspe J, Everett E, Braylan RC. Reduced expression of CD20 antigen as a characteristic marker for chronic lymphocytic leukemia. Am J Hematol. 1992;40:259–63.

    Article  CAS  PubMed  Google Scholar 

  46. Golay J, Lazzari M, Facchinetti V, Bernasconi S, Borleri G, Barbui T, Rambaldi A, Introna M. CD20 levels determine the in vitro susceptibility to rituximab and complement of B-cell chronic lymphocytic leukemia: further regulation by CD55 and CD59. Blood. 2001;98:3383–9.

    Article  CAS  PubMed  Google Scholar 

  47. van Meerten T, van Rijn RS, Hol S, Hagenbeek A, Ebeling SB. Complement-induced cell death by rituximab depends on CD20 expression level and acts complementary to antibody-dependent cellular cytotoxicity. Clin Cancer Res. 2006;12:4027–35.

    Article  PubMed  Google Scholar 

  48. Golay J, Zaffaroni L, Vaccari T, Lazzari M, Borleri GM, Bernasconi S, Tedesco F, Rambaldi A, Introna M. Biologic response of B lymphoma cells to anti-CD20 monoclonal antibody rituximab in vitro: CD55 and CD59 regulate complement-mediated cell lysis. Blood. 2000;95:3900–8.

    CAS  PubMed  Google Scholar 

  49. Iagaru A, Gambhir SS, Goris ML. 90Y-ibritumomab therapy in refractory non-Hodgkin’s lymphoma: observations from 111In-ibritumomab pretreatment imaging. J Nucl Med. 2008;49:1809–12.

    Article  PubMed  Google Scholar 

  50. Davis TA, Czerwinski DK, Levy R. Therapy of B-cell lymphoma with anti-CD20 antibodies can result in the loss of CD20 antigen expression. Clin Cancer Res. 1999;5:611–5.

    CAS  PubMed  Google Scholar 

  51. Jilani I, O’Brien S, Manshuri T, Thomas DA, Thomazy VA, Imam M, Naeem S, Verstovsek S, Kantarjian H, Giles F, Keating M, Albitar M. Transient down-modulation of CD20 by rituximab in patients with chronic lymphocytic leukemia. Blood. 2003;102:3514–20.

    Article  CAS  PubMed  Google Scholar 

  52. Hiraga J, Tomita A, Sugimoto T, Shimada K, Ito M, Nakamura S, Kiyoi H, Kinoshita T, Naoe T. Down-regulation of CD20 expression in B-cell lymphoma cells after treatment with rituximab-containing combination chemotherapies: its prevalence and clinical significance. Blood. 2009;113:4885–93.

    Article  CAS  PubMed  Google Scholar 

  53. Nakamaki T, Fukuchi K, Nakashima H, Ariizumi H, Maeda T, Saito B, Yanagisawa K, Tomoyasu S, Homma M, Shiozawa E, Yamochi-Onizuka T, Ota H. CD20 gene deletion causes a CD20-negative relapse in diffuse large B-cell lymphoma. Eur J Haematol. 2012;89:350–5.

    Article  PubMed  Google Scholar 

  54. Matsuda I, Hirota S. Bone marrow infiltration of CD20-negative follicular lymphoma after rituximab therapy: a histological mimicker of hematogones and B-cell acute lymphoblastic leukemia/lymphoma. Int J Clin Exp Pathol. 2015;8:9737–41.

    CAS  PubMed  PubMed Central  Google Scholar 

  55. Sugimoto T, Tomita A, Hiraga J, Shimada K, Kiyoi H, Kinoshita T, Naoe T. Escape mechanisms from antibody therapy to lymphoma cells: downregulation of CD20 mRNA by recruitment of the HDAC complex and not by DNA methylation. Biochem Biophy Res Commun. 2009;390:48–53.

    Article  CAS  Google Scholar 

  56. Terui Y, Mishima Y, Sugimura N, Kojima K, Sakurai T, Mishima Y, Kuniyoshi R, Taniyama A, Yokoyama M, Sakajiri S, Takeuchi K, Watanabe C, Takahashi S, Ito Y, Hatake K. Identification of CD20 C-terminal deletion mutations associated with loss of CD20 expression in non-Hodgkin’s lymphoma. Clin Cancer Res. 2009;15:2523–30.

    Article  CAS  PubMed  Google Scholar 

  57. Tsai PC, Hernandez-Ilizaliturri FJ, Bangia N, Olejniczak SH, Czuczman MS. Regulation of CD20 in rituximab-resistant cell lines and B-cell non-Hodgkin lymphoma. Clin Cancer Res. 2012;18:1039–50.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Czuczman MS, Olejniczak S, Gowda A, Kotowski A, Binder A, Kaur H, Knight J, Starostik P, Deans J, Hernandez-Ilizaliturri FJ. Acquirement of rituximab resistance in lymphoma cell lines is associated with both global CD20 gene and protein down-regulation regulated at the pretranscriptional and posttranscriptional levels. Clin Cancer Res. 2008;14:1561–70.

    Article  CAS  PubMed  Google Scholar 

  59. Venugopal P, Sivaraman S, Huang XK, Nayini J, Gregory SA, Preisler HD. Effects of cytokines on CD20 antigen expression on tumor cells from patients with chronic lymphocytic leukemia. Leuk Res. 2000;24(5):411.

    Article  CAS  PubMed  Google Scholar 

  60. Jahrsdörfer B, Hartmann G, Racila E, Jackson W, Mühlenhoff L, Meinhardt G, Endres S, Link BK, Krieg AM, Weiner GJ. CpG DNA increases primary malignant B cell expression of costimulatory molecules and target antigens. J Leukoc Biol. 2001;69:81–8.

    PubMed  Google Scholar 

  61. Hemmi H, Takeuchi O, Kawai T, Kaisho T, Sato S, Sanjo H, Matsumoto M, Hoshino K, Wagner H, Takeda K, Akira S. A Toll-like receptor recognizes bacterial DNA. Nature. 2000;408:740–5.

    Article  CAS  PubMed  Google Scholar 

  62. Krieg AM. Development of TLR9 agonists for cancer therapy. J Clin Invest. 2007;117:1184–94.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Hayashi K, Nagasaki E, Kan S, Ito M, Kamata Y, Homma S, Aiba K. Gemcitabine enhances rituximab-mediated complement-dependent cytotoxicity to B cell lymphoma by CD20 up-regulation. Cancer Sci. 2016. https://doi.org/10.1111/cas.12918. [Epub ahead of print].

  64. Wojciechowski W, Li H, Marshall S, Dell’Agnola C, Espinoza-Delgado I. Enhanced expression of CD20 in human tumor B cells is controlled through ERK-dependent mechanisms. J Immunol. 2005;174:7859–68.

    Article  CAS  PubMed  Google Scholar 

  65. Cragg MS, Glennie MJ. Antibody specificity controls in vivo effector mechanisms of anti-CD20 reagents. Blood. 2004;103:2738–43.

    Article  CAS  PubMed  Google Scholar 

  66. Tipton TR, Roghanian A, Oldham RJ, Carter MJ, Cox KL, Mockridge CI, French RR, Dahal LN, Duriez PJ, Hargreaves PG, Cragg MS, Beers SA. Antigenic modulation limits the effector cell mechanisms employed by type I anti-CD20 monoclonal antibodies. Blood. 2015;125:1901–9.

    Article  CAS  PubMed  Google Scholar 

  67. Lim SH, Vaughan AT, Ashton-Key M, Williams EL, Dixon SV, Chan HT, Beers SA, French RR, Cox KL, Davies AJ, Potter KN, Mockridge CI, Oscier DG, Johnson PW, Cragg MS, Glennie MJ. Fc gamma receptor IIb on target B cells promotes rituximab internalization and reduces clinical efficacy. Blood. 2011;118:2530–40.

    Article  PubMed  Google Scholar 

  68. Dransfield I. Inhibitory FcγRIIb and CD20 internalization. Blood. 2014;123:606–7.

    Article  CAS  PubMed  Google Scholar 

  69. Weng WK, Levy R. Two immunoglobulin G fragment C receptor polymorphisms independently predict response to rituximab in patients with follicular lymphoma. J Clin Oncol. 2003;21:3940–7.

    Article  CAS  PubMed  Google Scholar 

  70. Lam WA, Rosenbluth MJ, Fletcher DA. Chemotherapy exposure increases leukemia cell stiffness. Blood. 2007;109(8):3505.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. Li Y, Williams ME, Cousar JB, Pawluczkowycz AW, Lindorfer MA, Taylor RP. Rituximab-CD20 complexes are shaved from Z138 mantle cell lymphoma cells in intravenous and subcutaneous SCID mouse models. J Immunol. 2007;179:4263–71.

    Article  CAS  PubMed  Google Scholar 

  72. Beum PV, Peek EM, Lindorfer MA, Beurskens FJ, Engelberts PJ, Parren PW, van de Winkel JG, Taylor RP. Loss of CD20 and bound CD20 antibody from opsonized B cells occurs more rapidly because of trogocytosis mediated by Fc receptor-expressing effector cells than direct internalization by the B cells. J Immunol. 2011;187:3438–47.

    Article  CAS  PubMed  Google Scholar 

  73. Wang T, Zhang X, Li JJ. The role of NF-kappaB in the regulation of cell stress responses. Int Immunopharmacol. 2002;2:1509–20.

    Article  CAS  PubMed  Google Scholar 

  74. Xia Y, Shen S, Verma IM. NF-κB, an active player in human cancers. Cancer Immunol Res. 2014;2:823–30.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  75. Turturro F. Constitutive NF- κ B activation underlines major mechanism of drug resistance in relapsed refractory diffuse large B cell lymphoma. Biomed Res Int. 2015:ID484537.

    Google Scholar 

  76. Alizadeh AA, Eisen MB, Davis RE, Ma C, Lossos IS, Rosenwald A, Boldrick JC, Sabet H, Tran T, Yu X, Powell JI, Yang L, Marti GE, Moore T, Hudson J Jr, Lu L, Lewis DB, Tibshirani R, Sherlock G, Chan WC, Greiner TC, Weisenburger DD, Armitage JO, Warnke R, Levy R, Wilson W, Grever MR, Byrd JC, Botstein D, Brown PO, Staudt LM. Distinct types of diffuse large B-cell lymphoma identified by gene expression profiling. Nature. 2000;403:503–11.

    Article  CAS  PubMed  Google Scholar 

  77. Wilson WH, Jung SH, Porcu P, Hurd D, Johnson J, Martin SE, Czuczman M, Lai R, Said J, Chadburn A, Jones D, Dunleavy K, Canellos G, Zelenetz AD, Cheson BD, Hsi ED, Cancer Leukemia Group B. A Cancer and Leukemia Group B multi-center study of DA-EPOCH-rituximab in untreated diffuse large B-cell lymphoma with analysis of outcome by molecular subtype. Haematologica. 2012;97:758–65.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  78. Bohers E, Mareschal S, Bouzelfen A, Marchand V, Ruminy P, Maingonnat C, Ménard AL, Etancelin P, Bertrand P, Dubois S, Alcantara M, Bastard C, Tilly H, Jardin F. Targetable activating mutations are very frequent in GCB and ABC diffuse large B-cell lymphoma. Genes Chromosomes Cancer. 2014;53:144–53.

    Article  CAS  PubMed  Google Scholar 

  79. Fan M, Ahmed KM, Coleman MC, Spitz DR, Li JJ. Nuclear factor-kappaB and manganese superoxide dismutase mediate adaptive radioresistance in low-dose irradiated mouse skin epithelial cells. Cancer Res. 2007;67:3220–8.

    Article  CAS  PubMed  Google Scholar 

  80. Jazirehi AR, Huerta-Yepez S, Cheng G, Bonavida B. Rituximab (chimeric anti-CD20 monoclonal antibody) inhibits the constitutive nuclear factor-{kappa}B signaling pathway in non-Hodgkin’s lymphoma B-cell lines: role in sensitization to chemotherapeutic drug-induced apoptosis. Cancer Res. 2005;65:264–76.

    CAS  PubMed  Google Scholar 

  81. Odqvist L, Montes-Moreno S, Sánchez-Pacheco RE, Young KH, Martín-Sánchez E, Cereceda L, Sánchez-Verde L, Pajares R, Mollejo M, Fresno MF, Mazorra F, Ruíz-Marcellán C, Sánchez-Beato M, Piris MA. NFκB expression is a feature of both activated B-cell-like and germinal center B-cell-like subtypes of diffuse large B-cell lymphoma. Mod Pathol. 2014;27:1331–7.

    Article  CAS  PubMed  Google Scholar 

  82. Roschewski M, Staudt LM, Wilson WH. Diffuse large B-cell lymphoma-treatment approaches in the molecular era. Nat Rev Clin Oncol. 2014;11:12–23.

    Article  CAS  PubMed  Google Scholar 

  83. Di Bella N, Taetle R, Kolibaba K, Boyd T, Raju R, Barrera D, Cochran EW Jr, Dien PY, Lyons R, Schlegel PJ, Vukelja SJ, Boston J, Boehm KA, Wang Y, Asmar L. Results of a phase 2 study of bortezomib in patients with relapsed or refractory indolent lymphoma. Blood. 2010;115:475–80.

    Article  PubMed  CAS  Google Scholar 

  84. Coiffier B, Osmanov EA, Hong X, Scheliga A, Mayer J, Offner F, Rule S, Teixeira A, Walewski J, de Vos S, Crump M, Shpilberg O, Esseltine DL, Zhu E, Enny C, Theocharous P, van de Velde H, Elsayed YA, Zinzani PL, LYM-3001 Study Investigators. Bortezomib plus rituximab versus rituximab alone in patients with relapsed, rituximab-naive or rituximab-sensitive, follicular lymphoma: a randomised phase 3 trial. Lancet Oncol. 2011;12:773–84.

    Article  CAS  PubMed  Google Scholar 

  85. Fowler N, Kahl BS, Lee P, Matous JV, Cashen AF, Jacobs SA, Letzer J, Amin B, Williams ME, Smith S, Saleh A, Rosen P, Shi H, Parasuraman S, Cheson BD. Bortezomib, bendamustine, and rituximab in patients with relapsed or refractory follicular lymphoma: the phase II VERTICAL study. J Clin Oncol. 2011;29:3389–95.

    Article  CAS  PubMed  Google Scholar 

  86. Russo SM, Tepper JE, Baldwin AS Jr, Liu R, Adams J, Elliott P, Cusack JC Jr. Enhancement of radiosensitivity by proteasome inhibition: implications for a role of NF-kappaB. Int J Radiat Oncol Biol Phys. 2001;50:183–93.

    Article  CAS  PubMed  Google Scholar 

  87. Beaven AW, Shea TC, Moore DT, Feldman T, Ivanova A, Ferraro M, Ford P, Smith J, Goy A. A phase I study evaluating ibritumomab tiuxetan (Zevalin®) in combination with bortezomib (Velcade®) in relapsed/refractory mantle cell and low grade B-cell non-Hodgkin lymphoma. Leuk Lymphoma. 2012;53:254–8.

    Article  CAS  PubMed  Google Scholar 

  88. Roy R, Evens AM, Patton D, Gallot L, Larson A, Rademaker A, Cilley J, Spies S, Variakojis D, Gordon LI, Winter JN. Bortezomib may be safely combined with Y-90-ibritumomab tiuxetan in patients with relapsed/refractory follicular non-Hodgkin lymphoma: a phase I trial of combined induction therapy and bortezomib consolidation. Leuk Lymphoma. 2013;54:497–502.

    Article  CAS  PubMed  Google Scholar 

  89. Elstrom RL, Ruan J, Christos PJ, Martin P, Lebovic D, Osborne J, Goldsmith S, Greenberg J, Furman RR, Avram A, Putman R, Chapman E, Mazumdar M, Griffith K, Coleman M, Leonard JP, Kaminski MS. Phase 1 study of radiosensitization using bortezomib in patients with relapsed non-Hodgkin lymphoma receiving radioimmunotherapy with 131I-tositumomab. Leuk Lymphoma. 2015;56:342–6.

    Article  CAS  PubMed  Google Scholar 

  90. Goy A, Bernstein SH, Kahl BS, Djulbegovic B, Robertson MJ, de Vos S, Epner E, Krishnan A, Leonard JP, Lonial S, Nasta S, O’Connor OA, Shi H, Boral AL, Fisher RI. Bortezomib in patients with relapsed or refractory mantle cell lymphoma: updated time-to-event analyses of the multicenter phase 2 PINNACLE study. Ann Oncol. 2009;20:520–5.

    Article  CAS  PubMed  Google Scholar 

  91. Wang M, Oki Y, Pro B, Romaguera JE, Rodriguez MA, Samaniego F, McLaughlin P, Hagemeister F, Neelapu S, Copeland A, Samuels BI, Loyer EM, Ji Y, Younes A. Phase II study of yttrium-90-ibritumomab tiuxetan in patients with relapsed or refractory mantle cell lymphoma. J Clin Oncol. 2009;27:5213–8.

    Article  CAS  PubMed  Google Scholar 

  92. Kupperman E, Lee EC, Cao Y, Bannerman B, Fitzgerald M, Berger A, Yu J, Yang Y, Hales P, Bruzzese F, Liu J, Blank J, Garcia K, Tsu C, Dick L, Fleming P, Yu L, Manfredi M, Rolfe M, Bolen J. Evaluation of the proteasome inhibitor MLN9708 in preclinical models of human cancer. Cancer Res. 2010;70:1970–80.

    Article  CAS  PubMed  Google Scholar 

  93. Lee EC, Fitzgerald M, Bannerman B, Donelan J, Bano K, Terkelsen J, Bradley DP, Subakan O, Silva MD, Liu R, Pickard M, Li Z, Tayber O, Li P, Hales P, Carsillo M, Neppalli VT, Berger AJ, Kupperman E, Manfredi M, Bolen JB, Van Ness B, Janz S. Antitumor activity of the investigational proteasome inhibitor MLN9708 in mouse models of B-cell and plasma cell malignancies. Clin Cancer Res. 2011;17(23):7313.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  94. Assouline SE, Chang J, Cheson BD, Rifkin R, Hamburg S, Reyes R, Hui AM, Yu J, Gupta N, Di Bacco A, Shou Y, Martin P. Phase 1 dose-escalation study of IV ixazomib, an investigational proteasome inhibitor, in patients with relapsed/refractory lymphoma. Blood Cancer J. 2014;4:e251.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  95. Crespo J, Sun H, Welling TH, Tian Z, Zou W. T cell anergy, exhaustion, senescence, and stemness in the tumor microenvironment. Curr Opin Immunol. 2013;25:214–21.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  96. Lee Y, Auh SL, Wang Y, Burnette B, Wang Y, Meng Y, Beckett M, Sharma R, Chin R, Tu T, Weichselbaum RR, Fu YX. Therapeutic effects of ablative radiation on local tumor require CD8+ T cells: changing strategies for cancer treatment. Blood. 2009;114:589–95.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  97. Sahin U, Türeci O, Schmitt H, Cochlovius B, Johannes T, Schmits R, Stenner F, Luo G, Schobert I, Pfreundschuh M. Human neoplasms elicit multiple specific immune responses in the autologous host. Proc Natl Acad Sci U S A. 1995;92:11810–3.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  98. Céfai D, Favre L, Wattendorf E, Marti A, Jaggi R, Gimmi CD. Role of Fas ligand expression in promoting escape from immune rejection in a spontaneous tumor model. Int J Cancer. 2001;15(91):529–37.

    Article  Google Scholar 

  99. Afreen S, Dermime S. The immunoinhibitory B7-H1 molecule as a potential target in cancer: killing many birds with one stone. Hematol Oncol Stem Cell Ther. 2014;7:1–17.

    Article  PubMed  CAS  Google Scholar 

  100. Gajewski TF, Meng Y, Blank C, Brown I, Kacha A, Kline J, Harlin H. Immune resistance orchestrated by the tumor microenvironment. Immunol Rev. 2006;213:131–45.

    Article  CAS  PubMed  Google Scholar 

  101. Kim R, Emi M, Tanabe K, Uchida Y, Toge T. The role of Fas ligand and transforming growth factor beta in tumor progression: molecular mechanisms of immune privilege via Fas-mediated apoptosis and potential targets for cancer therapy. Cancer. 2004;100:2281–91.

    Article  CAS  PubMed  Google Scholar 

  102. Mannino MH, Zhu Z, Xiao H, Bai Q, Wakefield MR, Fang Y. The paradoxical role of IL-10 in immunity and cancer. Cancer Lett. 2015;367:103–7.

    Article  CAS  PubMed  Google Scholar 

  103. Munn DH, Mellor AL. Indoleamine 2,3 dioxygenase and metabolic control of immune responses. Trends Immunol. 2013;34:137–43.

    Article  CAS  PubMed  Google Scholar 

  104. Reits EA, Hodge JW, Herberts CA, Groothuis TA, Chakraborty M, Wansley EK, Camphausen K, Luiten RM, de Ru AH, Neijssen J, Griekspoor A, Mesman E, Verreck FA, Spits H, Schlom J, van Veelen P, Neefjes JJ. Radiation modulates the peptide repertoire, enhances MHC class I expression, and induces successful antitumor immunotherapy. J Exp Med. 2006;203:1259–71.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  105. Nishikawa H, Sakaguchi S. Regulatory T cells in tumor immunity. Int J Cancer. 2010;127:759–67.

    CAS  PubMed  Google Scholar 

  106. Marvel D, Gabrilovich DI. Myeloid-derived suppressor cells in the tumor microenvironment: expect the unexpected. J Clin Invest. 2015;125:3356–64.

    Article  PubMed  PubMed Central  Google Scholar 

  107. Sica A, Schioppa T, Mantovani A, Allavena P. Tumour-associated macrophages are a distinct M2 polarised population promoting tumour progression: potential targets of anti-cancer therapy. Eur J Cancer. 2006;42:717–27.

    Article  CAS  PubMed  Google Scholar 

  108. Schreiber RD, Old LJ, Smyth MJ. Cancer immunoediting: integrating immunity’s roles in cancer suppression and promotion. Science. 2011;331:1565–70.

    Article  CAS  PubMed  Google Scholar 

  109. Burnet FM. The concept of immunological surveillance. Prog Exp Tumor Res. 1970;13:1–27.

    Article  CAS  PubMed  Google Scholar 

  110. Swann JB, Smyth MJ. Immune surveillance of tumors. J Clin Investig. 2007;117:1137–46.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  111. Shankaran V, Ikeda H, Bruce AT, White JM, Swanson PE, Old LJ, Schreiber RD. IFNgamma and lymphocytes prevent primary tumour development and shape tumour immunogenicity. Nature. 2001;410:1107–11.

    Article  CAS  PubMed  Google Scholar 

  112. Muenst S, Läubli H, Soysal SD, Zippelius A, Tzankov A, Hoeller S. The immune system and cancer evasion strategies: therapeutic concepts. J Intern Med. 2016. https://doi.org/10.1111/joim.12470. [Epub ahead of print]Int Immunol 2016 Mar 22. pii: dxw015.

  113. Temizoz B, Kuroda E, Ishii KJ. Vaccine adjuvants as potential cancer immunotherapeutics. Int Immunol. 2016.; pii: dxw015. [Epub ahead of print].

    Google Scholar 

  114. Iwasaki A, Medzhitov R. Toll-like receptor control of the adaptive immune responses. Nat Immunol. 2004;5:987–95.

    Article  CAS  PubMed  Google Scholar 

  115. Bourke E, Bosisio D, Golay J, Polentarutti N, Mantovani A. The toll-like receptor repertoire of human B lymphocytes: inducible and selective expression of TLR9 and TLR10 in normal and transformed cells. Blood. 2003;102:956–63.

    Article  PubMed  Google Scholar 

  116. Link BK, Ballas ZK, Weisdorf D, Wooldridge JE, Bossler AD, Shannon M, Rasmussen WL, Krieg AM, Weiner GJ. Oligodeoxynucleotide CpG 7909 delivered as intravenous infusion demonstrates immunologic modulation in patients with previously treated non-Hodgkin lymphoma. J Immunother. 2006;29:558–68.

    Article  CAS  PubMed  Google Scholar 

  117. Brody JD, Ai WZ, Czerwinski DK, Torchia JA, Levy M, Advani RH, Kim YH, Hoppe RT, Knox SJ, Shin LK, Wapnir I, Tibshirani RJ, Levy R. In situ vaccination with a TLR9 agonist induces systemic lymphoma regression: a phase I/II study. J Clin Oncol. 2010;28:4324–32.

    Article  PubMed  PubMed Central  Google Scholar 

  118. Zent CS, Smith BJ, Ballas ZK, Wooldridge JE, Link BK, Call TG, Shanafelt TD, Bowen DA, Kay NE, Witzig TE, Weiner GJ. Phase I clinical trial of CpG oligonucleotide 7909 (PF-03512676) in patients with previously treated chronic lymphocytic leukemia. Leuk Lymphoma. 2012;53:211–7.

    Article  CAS  PubMed  Google Scholar 

  119. Witzig TE, Wiseman GA, Maurer MJ, Habermann TM, Micallef IN, Nowakowski GS, Ansell SM, Colgan JP, Inwards DJ, Porrata LF, Link BK, Zent CS, Johnston PB, Shanafelt TD, Allmer C, Asmann YW, Gupta M, Ballas ZK, Smith BJ, Weiner GJ. A phase I trial of immunostimulatory CpG 7909 oligodeoxynucleotide and 90 yttrium ibritumomab tiuxetan radioimmunotherapy for relapsed B-cell non-Hodgkin lymphoma. Am J Hematol. 2013;88:589–93.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  120. Jahrsdörfer B, Hartmann G, Racila E, Jackson W, Mühlenhoff L, Meinhardt G, Endres S, Link BK, Krieg AM, Weiner GJ. CpG DNA increases primary malignant B cell expression of costimulatory molecules and target antigens. J Leuk Biol. 2001;69:81–8.

    Google Scholar 

  121. Watts C, West MA, Zaru R. TLR signalling regulated antigen presentation in dendritic cells. Curr Opin Immunol. 2010;22:124–30.

    Article  CAS  PubMed  Google Scholar 

  122. Iwasaki A, Medzhitov R. Regulation of adaptive immunity by the innate immune system. Science. 2010;327:291–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  123. Decker T, Schneller F, Sparwasser T, Tretter T, Lipford GB, Wagner H, Peschel C. Immunostimulatory CpG-oligonucleotides cause proliferation, cytokine production, and an immunogenic phenotype in chronic lymphocytic leukemia B cells. Blood. 2000;95:999–1006.

    CAS  PubMed  Google Scholar 

  124. Demaria S, Ng B, Devitt ML, Babb JS, Kawashima N, Liebes L, Formenti SC. Ionizing radiation inhibition of distant untreated tumors (abscopal effect) is immune mediated. Int J Radiat Oncol Biol Phys. 2004;58:862–70.

    Article  PubMed  Google Scholar 

  125. Dewan MZ, Galloway AE, Kawashima N, Dewyngaert JK, Babb JS, Formenti SC, Demaria S. Fractionated but not single-dose radiotherapy induces an immune-mediated abscopal effect when combined with anti-CTLA-4 antibody. Clin Cancer Res. 2009;15:5379–88.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  126. Formenti SC, Demaria S. Combining radiotherapy and cancer immunotherapy: a paradigm shift. J Natl Cancer Inst. 2013;105:256–65.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  127. Lugade AA, Moran JP, Gerber SA, Rose RC, Frelinger JG, Lord EM. Local radiation therapy of B16 melanoma tumors increases the generation of tumor antigen-specific effector cells that traffic to the tumor. J Immunol. 2005;174:7516–23.

    Article  CAS  PubMed  Google Scholar 

  128. Gerber SA, Sedlacek AL, Cron KR, Murphy SP, Frelinger JG, Lord EM. IFN-γ mediates the antitumor effects of radiation therapy in a murine colon tumor. Am J Pathol. 2013;182:2345–54.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  129. Demaria S, Kawashima N, Yang AM, Devitt ML, Babb JS, Allison JP, Formenti SC. Immune-mediated inhibition of metastases after treatment with local radiation and CTLA-4 blockade in a mouse model of breast cancer. Clin Cancer Res. 2005;11:728–34.

    CAS  PubMed  Google Scholar 

  130. Ma Y, Kepp O, Ghiringhelli F, Apetoh L, Aymeric L, Locher C, Tesniere A, Martins I, Ly A, Haynes NM, Smyth MJ, Kroemer G, Zitvogel L. Chemotherapy and radiotherapy: cryptic anticancer vaccines. Semin Immunol. 2010;22:113–24.

    Article  CAS  PubMed  Google Scholar 

  131. Filatenkov A, Baker J, Mueller AM, Kenkel J, Ahn GO, Dutt S, Zhang N, Kohrt H, Jensen K, Dejbakhsh-Jones S, Shizuru JA, Negrin RN, Engleman EG, Strober S. Ablative tumor radiation can change the tumor immune cell microenvironment to induce durable complete remissions. Clin Cancer Res. 2015;21:3727–39.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  132. Song CW, Rhee JG, Kim T, Kersey JH, Levitt SH. Effect of x-irradiation on immunocompetency of T-lymphocytes. Cancer Clin Trials. 1981;4:331–42.

    CAS  PubMed  Google Scholar 

  133. Rosen EM, Fan S, Rockwell S, Goldberg ID. The molecular and cellular basis of radiosensitivity: implications for understanding how normal tissues and tumors respond to therapeutic radiation. Cancer Investig. 1999;17:56–72.

    Article  CAS  Google Scholar 

  134. Dovedi SJ, Adlard AL, Lipowska-Bhalla G, McKenna C, Jones S, Cheadle EJ, Stratford IJ, Poon E, Morrow M, Stewart R, Jones H, Wilkinson RW, Honeychurch J, Illidge TM. Acquired resistance to fractionated radiotherapy can be overcome by concurrent PD-L1 blockade. Cancer Res. 2014;74:5458–68.

    Article  CAS  PubMed  Google Scholar 

  135. Gandhi SJ, Minn AJ, Vonderheide RH, Wherry EJ, Hahn SM, Maity A. Awakening the immune system with radiation: Optimal dose and fractionation. Cancer Lett. 2015;368:185–90.

    Article  CAS  PubMed  Google Scholar 

  136. Chen L, Flies DB. Molecular mechanisms of T cell co-stimulation and co-inhibition. Nat Rev Immunol. 2013;13:227–42.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  137. Shin DS, Ribas A. The evolution of checkpoint blockade as a cancer therapy: what’s here, what’s next? Curr Opin Immunol. 2015;33:23–35.

    Article  CAS  PubMed  Google Scholar 

  138. Wu L, Wu MO, De la Maza L, Yun Z, Yu J, Zhao Y, Cho J, de Perrot M. Targeting the inhibitory receptor CTLA-4 on T cells increased abscopal effects in murine mesothelioma model. Oncotarget. 2015;6:12468–80.

    PubMed  PubMed Central  Google Scholar 

  139. Deng L, Liang H, Burnette B, Beckett M, Darga T, Weichselbaum RR, Fu YX. Irradiation and anti-PD-L1 treatment synergistically promote antitumor immunity in mice. J Clin Invest. 2014;124:687–95.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  140. Sharabi AB, Nirschl CJ, Kochel CM, Nirschl TR, Francica BJ, Velarde E, Deweese TL, Drake CG. Stereotactic radiation therapy augments antigen-specific PD-1-mediated antitumor immune responses via cross-presentation of tumor Antigen. Cancer Immunol Res. 2015;3:345–55.

    Article  CAS  PubMed  Google Scholar 

  141. Twyman-Saint Victor C, Rech AJ, Maity A, Rengan R, Pauken KE, Stelekati E, Benci JL, Xu B, Dada H, Odorizzi PM, Herati RS, Mansfield KD, Patsch D, Amaravadi RK, Schuchter LM, Ishwaran H, Mick R, Pryma DA, Xu X, Feldman MD, Gangadhar TC, Hahn SM, Wherry EJ, Vonderheide RH, Minn AJ. Radiation and dual checkpoint blockade activate non-redundant immune mechanisms in cancer. Nature. 2015;520:373–7.

    Article  CAS  PubMed  Google Scholar 

  142. Kwon ED, Drake CG, Scher HI, Fizazi K, Bossi A, van den Eertwegh AJ, Krainer M, Houede N, Santos R, Mahammedi H, Ng S, Maio M, Franke FA, Sundar S, Agarwal N, Bergman AM, Ciuleanu TE, Korbenfeld E, Sengeløv L, Hansen S, Logothetis C, Beer TM, McHenry MB, Gagnier P, Liu D, Gerritsen WR, CA184-043 Investigators. Ipilimumab versus placebo after radiotherapy in patients with metastatic castration-resistant prostate cancer that had progressed after docetaxel chemotherapy (CA184-043): a multicentre, randomised, double-blind, phase 3 trial. Lancet Oncol. 2014;15:700–12.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  143. Mathew M, Tam M, Ott PA, Pavlick AC, Rush SC, Donahue BR, Golfinos JG, Parker EC, Huang PP, Narayana A. Ipilimumab in melanoma with limited brain metastases treated with stereotactic radiosurgery. Melanoma Res. 2013;23:191–5.

    Article  CAS  PubMed  Google Scholar 

  144. Alomari AK, Cohen J, Vortmeyer AO, Chiang A, Gettinger S, Goldberg SB, Kluger HM, Chiang VL. Possible interaction of anti-PD-1 therapy with the effects of radiosurgery on brain metastases. Cancer Immunol Res 2016. pii: canimm.0238.2015. [Epub ahead of print].

    Google Scholar 

  145. Ahmed KA, Stallworth DG, Kim Y, Johnstone PA, Harrison LB, Caudell JJ, Yu HH, Etame AB, Weber JS, Gibney GT. Clinical outcomes of melanoma brain metastases treated with stereotactic radiation and anti-PD-1 therapy. Ann Oncol. 2016;27:434–41.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

We are indebted to Professors M Harada and K Tamada for their helpful discussions about the immunological cell death and the immune checkpoint blockade therapy.

Conflict of Interest

No conflict statement: No potential conflicts of interest were disclosed.

Author information

Authors and Affiliations

  1. Department of Diagnostic Radiology and Nuclear Medicine, Tokyo Women’s Medical University, Tokyo, Japan

    Koichiro Abe

Authors
  1. Koichiro Abe
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Koichiro Abe .

Editor information

Editors and Affiliations

  1. Institute of Advanced Clinical Medicine, Kindai University Faculty of Medicine, Osaka, Japan

    Makoto Hosono

  2. GIP Arronax, Nantes-Saint-Herblain, France

    Jean-François Chatal

Rights and permissions

Reprints and permissions

Copyright information

© 2018 Springer International Publishing AG, part of Springer Nature

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Abe, K. (2018). Resistance to Y-90 Ibritumomab Tiuxetan Therapy. In: Hosono, M., Chatal, JF. (eds) Resistance to Ibritumomab in Lymphoma. Resistance to Targeted Anti-Cancer Therapeutics, vol 18. Springer, Cham. https://doi.org/10.1007/978-3-319-78238-6_3

Download citation

Publish with us

Policies and ethics

Search

Navigation