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Cancer Immunology, Immunotherapy

, Volume 68, Issue 11, pp 1747–1757 | Cite as

Potential clinical application of tumor-infiltrating lymphocyte therapy for ovarian epithelial cancer prior or post-resistance to chemotherapy

  • Donastas Sakellariou-Thompson
  • Marie-Andrée Forget
  • Emily Hinchcliff
  • Joseph Celestino
  • Patrick Hwu
  • Amir A. Jazaeri
  • Cara HaymakerEmail author
  • Chantale BernatchezEmail author
Original Article

Abstract

Background

Immunotherapy has become a powerful treatment option for several solid tumor types. The presence of tumor-infiltrating lymphocytes (TIL) is correlated with better prognosis in ovarian cancer, pointing at the possibility to benefit from harnessing their anti-tumor activity. This preclinical study explores the feasibility of adoptive cell therapy (ACT) with TIL using an improved culture method.

Methods

TIL from high-grade serous ovarian cancer were cultured using a combination of IL-2 with agonistic antibodies targeting 4-1BB and CD3. The cells were phenotyped using flow cytometry in the fresh tissue and after expansion. Tumor reactivity was assessed against HLA-matched ovarian cancer cell lines via IFN-γ ELISPOT.

Results

Ovarian cancer is highly infiltrated with CD8+ TIL that are preferentially and robustly expanded with the addition of the agonistic antibodies. With a 95% success rate, the TIL are grown to ≥ 100 × 106 cells in 2–3 weeks without over differentiation. In addition, the CD8+ TIL grown with this method showed HLA-restricted tumor recognition.

Conclusions

These results indicate the viability of TIL ACT for refractory ovarian cancer by allowing for the large expansion of anti-tumor TIL in a short time and consistent manner.

Keywords

Ovarian cancer Tumor-infiltrating lymphocytes TIL therapy Adoptive cell therapy 

Abbreviations

BTLA

B- and T-lymphocyte attenuator

OvCa

Epithelial ovarian cancer

MDACC

MD Anderson Cancer Center

ORR

Overall response rate

TIL-CM

Tumor-infiltrating lymphocyte complete medium

TRM

Tissue-resident memory T cell

Notes

Acknowledgements

The authors wish to acknowledge the patients who consented to tissue procurement for research and their caregivers. Thank you to Bristol-Myers Squibb for providing Urelumab and Prometheus for the IL-2. The authors would like to thank René J. Tavera for his early contributions to culturing OvCa TIL.

Author contributions

DST conducted all the experiments and data analysis. DST and MAF generated the TIL lines and prepared the figures. DST, MAF, CH, and CB were responsible for writing the manuscript, while all authors contributed to manuscript editing and approved the final manuscript version. JC oversaw the consent and collection of human samples. MAF, CH, and CB helped with interpretation of the data. JC, EH, and AAJ helped with patients’ clinical information. PH and AAJ provided support and guidance for the study. DST, MAF, CH, and CB designed the experiments and the conceptual design of the study.

Funding

This research was supported in part by the MD Anderson Cancer Center Support Grant (P30 CA016672), a T32 training grant for gynecologic oncology (CA101642), the MD Anderson Ovarian Cancer Moon Shot program, and an MD Anderson Institutional Research Grant (Amir A. Jazaeri). We also acknowledge the support of the Flow Cytometry and Cellular Imaging, Research Histology, and Characterized Cell Line cores which are also supported by the support grant (P30 CA016672).

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

All procedures performed were in accordance with the 1975 Helsinki declaration. Ethical approval and tissue from surgical resections used to expand TIL were both obtained under protocols (PA16-0912 and LAB02-188) approved by the Institutional Review Board of The University of Texas MD Anderson Cancer Center.

Informed consent

Written informed consent was obtained from all individual participants included in the study for their specimens and data to be used in research and for publication.

Cell line authentication

COV318 and COV362 were originally purchased from Sigma–Aldrich (now Millipore-Sigma, St. Louis, MO) and SKOV3 from the American Type Culture Collection (ATCC, Manassas, VA). All OvCa cell lines were HLA-typed, STR fingerprinted, and confirmed mycoplasma-free at MDACC.

Supplementary material

262_2019_2402_MOESM1_ESM.pdf (1.1 mb)
Supplementary material 1 (PDF 1135 kb)

References

  1. 1.
    Siegel RL, Miller KD (2018) Jemal A (2018) cancer statistics. CA Cancer J Clin 68(1):7–30.  https://doi.org/10.3322/caac.21442 CrossRefGoogle Scholar
  2. 2.
    Zsiros E, Tanyi J, Balint K, Kandalaft LE (2014) Immunotherapy for ovarian cancer: recent advances and perspectives. Curr Opin Oncol 26(5):492–500.  https://doi.org/10.1097/CCO.0000000000000111 CrossRefGoogle Scholar
  3. 3.
    Vaughan S, Coward JI, Bast RC Jr, Berchuck A, Berek JS, Brenton JD, Coukos G, Crum CC, Drapkin R, Etemadmoghadam D, Friedlander M, Gabra H, Kaye SB, Lord CJ, Lengyel E, Levine DA, McNeish IA, Menon U, Mills GB, Nephew KP, Oza AM, Sood AK, Stronach EA, Walczak H, Bowtell DD, Balkwill FR (2011) Rethinking ovarian cancer: recommendations for improving outcomes. Nat Rev Cancer 11(10):719–725.  https://doi.org/10.1038/nrc3144 CrossRefPubMedPubMedCentralGoogle Scholar
  4. 4.
    Leitao MM, Chi DS (2009) Surgical management of recurrent ovarian cancer. Semin Oncol 36(2):106–111.  https://doi.org/10.1053/j.seminoncol.2008.12.002 CrossRefGoogle Scholar
  5. 5.
    Ding M, Mei-jiao G (1991) Immune effect of tumor-infiltrating lymphocytes and its relation to the survival rate of patients with ovarian malignancies. J Tongji Med Univ 11(4):5CrossRefGoogle Scholar
  6. 6.
    Zhang L, Conejo-Garcia JR, Katsaros D, Gimotty PA, Massobrio M, Regnani G, Makrigiannakis A, Gray H, Schlienger K, Liebman MN, Rubin SC, Coukos G (2003) Intratumoral T cells, recurrence, and survival in epithelial ovarian cancer. N Engl J Med 348(3):203–213.  https://doi.org/10.1056/NEJMoa020177 CrossRefGoogle Scholar
  7. 7.
    Sato E, Olson SH, Ahn J, Bundy B, Nishikawa H, Qian F, Jungbluth AA, Frosina D, Gnjatic S, Ambrosone C, Kepner J, Odunsi T, Ritter G, Lele S, Chen YT, Ohtani H, Old LJ, Odunsi K (2005) Intraepithelial CD8+ tumor-infiltrating lymphocytes and a high CD8+/regulatory T cell ratio are associated with favorable prognosis in ovarian cancer. Proc Natl Acad Sci USA 102(51):18538–18543.  https://doi.org/10.1073/pnas.0509182102 CrossRefPubMedPubMedCentralGoogle Scholar
  8. 8.
    Leffers N, Gooden MJ, de Jong RA, Hoogeboom BN, ten Hoor KA, Hollema H, Boezen HM, van der Zee AG, Daemen T, Nijman HW (2009) Prognostic significance of tumor-infiltrating T-lymphocytes in primary and metastatic lesions of advanced stage ovarian cancer. Cancer Immunol Immunother 58(3):449–459.  https://doi.org/10.1007/s00262-008-0583-5 CrossRefGoogle Scholar
  9. 9.
    Nielsen JS, Sahota RA, Milne K, Kost SE, Nesslinger NJ, Watson PH, Nelson BH (2012) CD20+ tumor-infiltrating lymphocytes have an atypical CD27 memory phenotype and together with CD8+ T cells promote favorable prognosis in ovarian cancer. Clin Cancer Res 18(12):3281–3292.  https://doi.org/10.1158/1078-0432.CCR-12-0234 CrossRefGoogle Scholar
  10. 10.
    Ino Y, Yamazaki-Itoh R, Shimada K, Iwasaki M, Kosuge T, Kanai Y, Hiraoka N (2013) Immune cell infiltration as an indicator of the immune microenvironment of pancreatic cancer. Br J Cancer 108(4):914–923.  https://doi.org/10.1038/bjc.2013.32 CrossRefPubMedPubMedCentralGoogle Scholar
  11. 11.
    Fukunaga A, Miyamoto M, Cho Y, Murakami S, Kawarada Y, Oshikiri T, Kato K, Kurokawa T, Suzuoki M, Nakakubo Y, Hiraoka K, Itoh T, Morikawa T, Okushiba S, Kondo S, Katoh H (2004) CD8+ Tumor-infiltrating lymphocytes together with CD4+ tumor-infiltrating lymphocytes and dendritic cells improve the prognosis of patients with pancreatic adenocarcinoma. Pancreas 28(1):e26–e31.  https://doi.org/10.1097/00006676-200401000-00023 CrossRefPubMedPubMedCentralGoogle Scholar
  12. 12.
    Hodi FS, O’Day SJ, McDermott DF, Weber RW, Sosman JA, Haanen JB, Gonzalez R, Robert C, Schadendorf D, Hassel JC, Akerley W, van den Eertwegh AJ, Lutzky J, Lorigan P, Vaubel JM, Linette GP, Hogg D, Ottensmeier CH, Lebbe C, Peschel C, Quirt I, Clark JI, Wolchok JD, Weber JS, Tian J, Yellin MJ, Nichol GM, Hoos A, Urba WJ (2010) Improved survival with ipilimumab in patients with metastatic melanoma. N Engl J Med 363(8):711–723.  https://doi.org/10.1056/NEJMoa1003466 CrossRefPubMedPubMedCentralGoogle Scholar
  13. 13.
    Topalian SL, Sznol M, McDermott DF, Kluger HM, Carvajal RD, Sharfman WH, Brahmer JR, Lawrence DP, Atkins MB, Powderly JD, Leming PD, Lipson EJ, Puzanov I, Smith DC, Taube JM, Wigginton JM, Kollia GD, Gupta A, Pardoll DM, Sosman JA, Hodi FS (2014) Survival, durable tumor remission, and long-term safety in patients with advanced melanoma receiving nivolumab. J Clin Oncol 32(10):1020–1030.  https://doi.org/10.1200/JCO.2013.53.0105 CrossRefPubMedPubMedCentralGoogle Scholar
  14. 14.
    Larkin J, Chiarion-Sileni V, Gonzalez R, Grob JJ, Cowey CL, Lao CD, Schadendorf D, Dummer R, Smylie M, Rutkowski P, Ferrucci PF, Hill A, Wagstaff J, Carlino MS, Haanen JB, Maio M, Marquez-Rodas I, McArthur GA, Ascierto PA, Long GV, Callahan MK, Postow MA, Grossmann K, Sznol M, Dreno B, Bastholt L, Yang A, Rollin LM, Horak C, Hodi FS, Wolchok JD (2015) Combined nivolumab and ipilimumab or monotherapy in untreated melanoma. N Engl J Med 373(1):23–34.  https://doi.org/10.1056/NEJMoa1504030 CrossRefPubMedPubMedCentralGoogle Scholar
  15. 15.
    Wolchok JD, Kluger H, Callahan MK, Postow MA, Rizvi NA, Lesokhin AM, Segal NH, Ariyan CE, Gordon RA, Reed K, Burke MM, Caldwell A, Kronenberg SA, Agunwamba BU, Zhang X, Lowy I, Inzunza HD, Feely W, Horak CE, Hong Q, Korman AJ, Wigginton JM, Gupta A, Sznol M (2013) Nivolumab plus ipilimumab in advanced melanoma. N Engl J Med 369(2):122–133.  https://doi.org/10.1056/NEJMoa1302369 CrossRefPubMedPubMedCentralGoogle Scholar
  16. 16.
    Schachter J, Ribas A, Long GV, Arance A, Grob J-J, Mortier L, Daud A, Carlino MS, McNeil C, Lotem M, Larkin J, Lorigan P, Neyns B, Blank C, Petrella TM, Hamid O, Zhou H, Ebbinghaus S, Ibrahim N, Robert C (2017) Pembrolizumab versus ipilimumab for advanced melanoma: final overall survival results of a multicentre, randomised, open-label phase 3 study (KEYNOTE-006). The Lancet 390(10105):1853–1862.  https://doi.org/10.1016/s0140-6736(17)31601-x CrossRefGoogle Scholar
  17. 17.
    Brahmer J, Reckamp KL, Baas P, Crino L, Eberhardt WE, Poddubskaya E, Antonia S, Pluzanski A, Vokes EE, Holgado E, Waterhouse D, Ready N, Gainor J, Aren Frontera O, Havel L, Steins M, Garassino MC, Aerts JG, Domine M, Paz-Ares L, Reck M, Baudelet C, Harbison CT, Lestini B, Spigel DR (2015) Nivolumab versus docetaxel in advanced squamous-cell non-small-cell lung cancer. N Engl J Med 373(2):123–135.  https://doi.org/10.1056/NEJMoa1504627 CrossRefPubMedPubMedCentralGoogle Scholar
  18. 18.
    Antonia S, Goldberg SB, Balmanoukian A, Chaft JE, Sanborn RE, Gupta A, Narwal R, Steele K, Gu Y, Karakunnel JJ, Rizvi NA (2016) Safety and antitumour activity of durvalumab plus tremelimumab in non-small cell lung cancer: a multicentre, phase 1b study. Lancet Oncol 17(3):299–308.  https://doi.org/10.1016/s1470-2045(15)00544-6 CrossRefPubMedPubMedCentralGoogle Scholar
  19. 19.
    Motzer RJ, Escudier B, McDermott DF, George S, Hammers HJ, Srinivas S, Tykodi SS, Sosman JA, Procopio G, Plimack ER, Castellano D, Choueiri TK, Gurney H, Donskov F, Bono P, Wagstaff J, Gauler TC, Ueda T, Tomita Y, Schutz FA, Kollmannsberger C, Larkin J, Ravaud A, Simon JS, Xu LA, Waxman IM, Sharma P, CheckMate I (2015) Nivolumab versus everolimus in advanced renal-cell carcinoma. N Engl J Med 373(19):1803–1813.  https://doi.org/10.1056/NEJMoa1510665 CrossRefPubMedPubMedCentralGoogle Scholar
  20. 20.
    Hodi FS, Butler M, Oble DA, Seiden MV, Haluska FG, Kruse A, Macrae S, Nelson M, Canning C, Lowy I, Korman A, Lautz D, Russell S, Jaklitsch MT, Ramaiya N, Chen TC, Neuberg D, Allison JP, Mihm MC, Dranoff G (2008) Immunologic and clinical effects of antibody blockade of cytotoxic T lymphocyte-associated antigen 4 in previously vaccinated cancer patients. Proc Natl Acad Sci USA 105(8):3005–3010.  https://doi.org/10.1073/pnas.0712237105 CrossRefPubMedPubMedCentralGoogle Scholar
  21. 21.
    Hamanishi J, Mandai M, Ikeda T, Minami M, Kawaguchi A, Murayama T, Kanai M, Mori Y, Matsumoto S, Chikuma S, Matsumura N, Abiko K, Baba T, Yamaguchi K, Ueda A, Hosoe Y, Morita S, Yokode M, Shimizu A, Honjo T, Konishi I (2015) Safety and antitumor activity of anti-PD-1 antibody, nivolumab, in patients with platinum-resistant ovarian cancer. J Clin Oncol 33(34):4015–4022.  https://doi.org/10.1200/JCO.2015.62.3397 CrossRefPubMedPubMedCentralGoogle Scholar
  22. 22.
    Brahmer JR, Tykodi SS, Chow LQ, Hwu WJ, Topalian SL, Hwu P, Drake CG, Camacho LH, Kauh J, Odunsi K, Pitot HC, Hamid O, Bhatia S, Martins R, Eaton K, Chen S, Salay TM, Alaparthy S, Grosso JF, Korman AJ, Parker SM, Agrawal S, Goldberg SM, Pardoll DM, Gupta A, Wigginton JM (2012) Safety and activity of anti-PD-L1 antibody in patients with advanced cancer. N Engl J Med 366(26):2455–2465.  https://doi.org/10.1056/NEJMoa1200694 CrossRefPubMedPubMedCentralGoogle Scholar
  23. 23.
    Rosenberg SA, Yang JC, Sherry RM, Kammula US, Hughes MS, Phan GQ, Citrin DE, Restifo NP, Robbins PF, Wunderlich JR, Morton KE, Laurencot CM, Steinberg SM, White DE, Dudley ME (2011) Durable complete responses in heavily pretreated patients with metastatic melanoma using T-cell transfer immunotherapy. Clin Cancer Res 17(13):4550–4557.  https://doi.org/10.1158/1078-0432.CCR-11-0116 CrossRefPubMedPubMedCentralGoogle Scholar
  24. 24.
    Besser MJ, Shapira-Frommer R, Treves AJ, Zippel D, Itzhaki O, Hershkovitz L, Levy D, Kubi A, Hovav E, Chermoshniuk N, Shalmon B, Hardan I, Catane R, Markel G, Apter S, Ben-Nun A, Kuchuk I, Shimoni A, Nagler A, Schachter J (2010) Clinical responses in a phase II study using adoptive transfer of short-term cultured tumor infiltration lymphocytes in metastatic melanoma patients. Clin Cancer Res 16(9):2646–2655.  https://doi.org/10.1158/1078-0432.CCR-10-0041 CrossRefGoogle Scholar
  25. 25.
    Radvanyi LG, Bernatchez C, Zhang M, Fox PS, Miller P, Chacon J, Wu R, Lizee G, Mahoney S, Alvarado G, Glass M, Johnson VE, McMannis JD, Shpall E, Prieto V, Papadopoulos N, Kim K, Homsi J, Bedikian A, Hwu WJ, Patel S, Ross MI, Lee JE, Gershenwald JE, Lucci A, Royal R, Cormier JN, Davies MA, Mansaray R, Fulbright OJ, Toth C, Ramachandran R, Wardell S, Gonzalez A, Hwu P (2012) Specific lymphocyte subsets predict response to adoptive cell therapy using expanded autologous tumor-infiltrating lymphocytes in metastatic melanoma patients. Clin Cancer Res 18(24):6758–6770.  https://doi.org/10.1158/1078-0432.CCR-12-1177 CrossRefPubMedPubMedCentralGoogle Scholar
  26. 26.
    Forget MA, Haymaker C, Hess KR, Meng YJ, Creasy C, Karpinets T, Fulbright OJ, Roszik J, Woodman SE, Kim YU, Sakellariou-Thompson D, Bhatta A, Wahl A, Flores E, Thorsen ST, Tavera RJ, Ramachandran R, Gonzalez AM, Toth CL, Wardell S, Mansaray R, Patel V, Carpio DJ, Vaughn C, Farinas CM, Velasquez PG, Hwu WJ, Patel SP, Davies MA, Diab A, Glitza IC, Tawbi H, Wong MK, Cain S, Ross MI, Lee JE, Gershenwald JE, Lucci A, Royal R, Cormier JN, Wargo JA, Radvanyi LG, Torres-Cabala CA, Beroukhim R, Hwu P, Amaria RN, Bernatchez C (2018) Prospective analysis of adoptive til therapy in patients with metastatic melanoma: response, impact of anti-CTLA4, and biomarkers to predict clinical outcome. Clin Cancer Res 24(18):4416–4428.  https://doi.org/10.1158/1078-0432.CCR-17-3649 CrossRefPubMedPubMedCentralGoogle Scholar
  27. 27.
    Aoki Y, Takakuwa K, Kodama S, Tanaka K, Takahashi M, Tokunaga A, Takahashi T (1991) Use of adoptive transfer of tumor-infiltrating lymphocytes alone or in combination with cisplatin-containing chemotherapy in patients with epithelial ovarian-cancer. Can Res 51(7):1934–1939Google Scholar
  28. 28.
    Freedman RS, Edwards CL, Kavanagh JJ, Kudelka AP, Katz RL, Carrasco CH, Atkinson EN, Scott W, Tomasovic B, Templin S et al (1994) Intraperitoneal adoptive immunotherapy of ovarian carcinoma with tumor-infiltrating lymphocytes and low-dose recombinant interleukin-2: a pilot trial. J Immunother Emphasis Tumor Immunol 16(3):198–210CrossRefGoogle Scholar
  29. 29.
    Ikarashi H, Fujita K, Takakuwa K, Kodama S, Tokunaga A, Takahashi T, Tanaka K (1994) Immunomodulation in patients with epithelial ovarian cancer after adoptive transfer of tumor-infiltrating lymphocytes. Cancer Res 54(1):190–196PubMedPubMedCentralGoogle Scholar
  30. 30.
    Fujita K, Ikarashi H, Takakuwa K, Kodama S, Tokunaga A, Takahashi T, Tanaka K (1995) Prolonged disease-free period in patients with advanced epithelial ovarian cancer after adoptive transfer of tumor-infiltrating lymphocytes. Clin Cancer Res 1(5):501–507Google Scholar
  31. 31.
    Freedman RS, Kudelka AP, Kavanagh JJ, Verschraegen C, Edwards CL, Nash M, Levy L, Atkinson EN, Zhang HZ, Melichar B, Patenia R, Templin S, Scott W, Platsoucas CD (2000) Clinical and biological effects of intraperitoneal injections of recombinant interferon-gamma and recombinant interleukin 2 with or without tumor-infiltrating lymphocytes in patients with ovarian or peritoneal carcinoma. Clin Cancer Res 6(6):2268–2278Google Scholar
  32. 32.
    Dudley ME, Yang JC, Sherry R, Hughes MS, Royal R, Kammula U, Robbins PF, Huang J, Citrin DE, Leitman SF, Wunderlich J, Restifo NP, Thomasian A, Downey SG, Smith FO, Klapper J, Morton K, Laurencot C, White DE, Rosenberg SA (2008) Adoptive cell therapy for patients with metastatic melanoma: evaluation of intensive myeloablative chemoradiation preparative regimens. J Clin Oncol 26(32):5233–5239.  https://doi.org/10.1200/JCO.2008.16.5449 CrossRefPubMedPubMedCentralGoogle Scholar
  33. 33.
    Chacon JA, Sarnaik AA, Chen JQ, Creasy C, Kale C, Robinson J, Weber J, Hwu P, Pilon-Thomas S, Radvanyi L (2015) Manipulating the tumor microenvironment ex vivo for enhanced expansion of tumor-infiltrating lymphocytes for adoptive cell therapy. Clin Cancer Res 21(3):611–621.  https://doi.org/10.1158/1078-0432.CCR-14-1934 CrossRefGoogle Scholar
  34. 34.
    Harao M, Forget MA, Roszik J, Gao H, Babiera GV, Krishnamurthy S, Chacon JA, Li S, Mittendorf EA, DeSnyder SM, Rockwood KF, Bernatchez C, Ueno NT, Radvanyi LG, Vence L, Haymaker C, Reuben JM (2017) 4-1BB-Enhanced Expansion of CD8+ TIL from triple-negative breast cancer unveils mutation-specific CD8+ T cells. Cancer Immunol Res 5(6):439–445.  https://doi.org/10.1158/2326-6066.CIR-16-0364 CrossRefPubMedPubMedCentralGoogle Scholar
  35. 35.
    Sakellariou-Thompson D, Forget MA, Creasy C, Bernard V, Zhao L, Kim YU, Hurd MW, Uraoka N, Parra ER, Kang Y, Bristow CA, Rodriguez-Canales J, Fleming JB, Varadhachary G, Javle M, Overman MJ, Alvarez HA, Heffernan TP, Zhang J, Hwu P, Maitra A, Haymaker C, Bernatchez C (2017) 4-1BB agonist focuses CD8(+) Tumor-infiltrating T-Cell growth into a distinct repertoire capable of tumor recognition in pancreatic cancer. Clin Cancer Res 23(23):7263–7275.  https://doi.org/10.1158/1078-0432.CCR-17-0831 CrossRefPubMedPubMedCentralGoogle Scholar
  36. 36.
    Tavera RJ, Forget MA, Kim YU, Sakellariou-Thompson D, Creasy CA, Bhatta A, Fulbright OJ, Ramachandran R, Thorsen ST, Flores E, Wahl A, Gonzalez AM, Toth C, Wardell S, Mansaray R, Radvanyi LG, Gombos DS, Patel SP, Hwu P, Amaria RN, Bernatchez C, Haymaker C (2018) Utilizing T-cell activation signals 1, 2, and 3 for tumor-infiltrating lymphocytes (TIL) expansion: the advantage over the sole use of interleukin-2 in cutaneous and uveal melanoma. J Immunother.  https://doi.org/10.1097/CJI.0000000000000230 CrossRefPubMedPubMedCentralGoogle Scholar
  37. 37.
    Forget MA, Malu S, Liu H, Toth C, Maiti S, Kale C, Haymaker C, Bernatchez C, Huls H, Wang E, Marincola FM, Hwu P, Cooper LJ, Radvanyi LG (2014) Activation and propagation of tumor-infiltrating lymphocytes on clinical-grade designer artificial antigen-presenting cells for adoptive immunotherapy of melanoma. J Immunother 37(9):448–460.  https://doi.org/10.1097/CJI.0000000000000056 CrossRefPubMedPubMedCentralGoogle Scholar
  38. 38.
    Moon BI, Kim TH, Seoh JY (2015) Functional modulation of regulatory T Cells by IL-2. PLoS One 10(11):e0141864.  https://doi.org/10.1371/journal.pone.0141864 CrossRefPubMedPubMedCentralGoogle Scholar
  39. 39.
    Haymaker CL, Wu RC, Ritthipichai K, Bernatchez C, Forget MA, Chen JQ, Liu H, Wang E, Marincola F, Hwu P, Radvanyi LG (2015) BTLA marks a less-differentiated tumor-infiltrating lymphocyte subset in melanoma with enhanced survival properties. Oncoimmunology 4(8):e1014246.  https://doi.org/10.1080/2162402X.2015.1014246 CrossRefPubMedPubMedCentralGoogle Scholar
  40. 40.
    Ritthipichai K, Haymaker CL, Martinez M, Aschenbrenner A, Yi X, Zhang M, Kale C, Vence LM, Roszik J, Hailemichael Y, Overwijk WW, Varadarajan N, Nurieva R, Radvanyi LG, Hwu P, Bernatchez C (2017) Multifaceted role of BTLA in the control of CD8(+) T-cell fate after antigen encounter. Clin Cancer Res 23(20):6151–6164.  https://doi.org/10.1158/1078-0432.CCR-16-1217 CrossRefPubMedPubMedCentralGoogle Scholar
  41. 41.
    Romero P, Zippelius A, Kurth I, Pittet MJ, Touvrey C, Iancu EM, Corthesy P, Devevre E, Speiser DE, Rufer N (2007) Four functionally distinct populations of human effector-memory CD8+ T lymphocytes. J Immunol 178(7):4112–4119.  https://doi.org/10.4049/jimmunol.178.7.4112 CrossRefPubMedPubMedCentralGoogle Scholar
  42. 42.
    Shin H, Wherry EJ (2007) CD8 T cell dysfunction during chronic viral infection. Curr Opin Immunol 19(4):408–415.  https://doi.org/10.1016/j.coi.2007.06.004 CrossRefPubMedPubMedCentralGoogle Scholar
  43. 43.
    Crome SQ, Nguyen LT, Lopez-Verges S, Yang SY, Martin B, Yam JY, Johnson DJ, Nie J, Pniak M, Yen PH, Milea A, Sowamber R, Katz SR, Bernardini MQ, Clarke BA, Shaw PA, Lang PA, Berman HK, Pugh TJ, Lanier LL, Ohashi PS (2017) A distinct innate lymphoid cell population regulates tumor-associated T cells. Nat Med 23(3):368–375.  https://doi.org/10.1038/nm.4278 CrossRefPubMedPubMedCentralGoogle Scholar
  44. 44.
    Webb JR, Milne K, Watson P, Deleeuw RJ, Nelson BH (2014) Tumor-infiltrating lymphocytes expressing the tissue resident memory marker CD103 are associated with increased survival in high-grade serous ovarian cancer. Clin Cancer Res 20(2):434–444.  https://doi.org/10.1158/1078-0432.CCR-13-1877 CrossRefPubMedPubMedCentralGoogle Scholar
  45. 45.
    Komdeur FL, Wouters MC, Workel HH, Tijans AM, Terwindt AL, Brunekreeft KL, Plat A, Klip HG, Eggink FA, Leffers N, Helfrich W, Samplonius DF, Bremer E, Wisman GB, Daemen T, Duiker EW, Hollema H, Nijman HW, de Bruyn M (2016) CD103 + intraepithelial T cells in high-grade serous ovarian cancer are phenotypically diverse TCRalphabeta + CD8alphabeta + T cells that can be targeted for cancer immunotherapy. Oncotarget 7(46):75130–75144.  https://doi.org/10.18632/oncotarget.12077 CrossRefPubMedPubMedCentralGoogle Scholar
  46. 46.
    Solberg OD, Mack SJ, Lancaster AK, Single RM, Tsai Y, Sanchez-Mazas A, Thomson G (2008) Balancing selection and heterogeneity across the classical human leukocyte antigen loci: a meta-analytic review of 497 population studies. Hum Immunol 69(7):443–464.  https://doi.org/10.1016/j.humimm.2008.05.001 CrossRefPubMedPubMedCentralGoogle Scholar
  47. 47.
    Yokokawa J, Palena C, Arlen P, Hassan R, Ho M, Pastan I, Schlom J, Tsang KY (2005) Identification of novel human CTL epitopes and their agonist epitopes of mesothelin. Clin Cancer Res 11(17):6342–6351.  https://doi.org/10.1158/1078-0432.CCR-05-0596 CrossRefPubMedPubMedCentralGoogle Scholar
  48. 48.
    Rahma OE, Ashtar E, Czystowska M, Szajnik ME, Wieckowski E, Bernstein S, Herrin VE, Shams MA, Steinberg SM, Merino M, Gooding W, Visus C, Deleo AB, Wolf JK, Bell JG, Berzofsky JA, Whiteside TL, Khleif SN (2012) A gynecologic oncology group phase II trial of two p53 peptide vaccine approaches: subcutaneous injection and intravenous pulsed dendritic cells in high recurrence risk ovarian cancer patients. Cancer Immunol Immunother 61(3):373–384.  https://doi.org/10.1007/s00262-011-1100-9 CrossRefPubMedPubMedCentralGoogle Scholar
  49. 49.
    Deniger DC, Pasetto A, Robbins PF, Gartner JJ, Prickett TD, Paria BC, Malekzadeh P, Jia L, Yossef R, Langhan MM, Wunderlich JR, Danforth DN, Somerville RPT, Rosenberg SA (2018) T-cell responses to TP53 “hotspot” mutations and unique neoantigens expressed by human ovarian cancers. Clin Cancer Res.  https://doi.org/10.1158/1078-0432.CCR-18-0573 CrossRefPubMedPubMedCentralGoogle Scholar
  50. 50.
    Hardwick NR, Frankel P, Ruel C, Kilpatrick J, Tsai W, Kos F, Kaltcheva T, Leong L, Morgan R, Chung V, Tinsley R, Eng M, Wilczynski S, Ellenhorn JDI, Diamond DJ, Cristea M (2018) p53-reactive T cells are associated with clinical benefit in patients with platinum-resistant epithelial ovarian cancer after treatment with a p53 vaccine and gemcitabine chemotherapy. Clin Cancer Res 24(6):1315–1325.  https://doi.org/10.1158/1078-0432.CCR-17-2709 CrossRefPubMedPubMedCentralGoogle Scholar
  51. 51.
    Odunsi K, Matsuzaki J, Karbach J, Neumann A, Mhawech-Fauceglia P, Miller A, Beck A, Morrison CD, Ritter G, Godoy H, Lele S, duPont N, Edwards R, Shrikant P, Old LJ, Gnjatic S, Jager E (2012) Efficacy of vaccination with recombinant vaccinia and fowlpox vectors expressing NY-ESO-1 antigen in ovarian cancer and melanoma patients. Proc Natl Acad Sci USA 109(15):5797–5802.  https://doi.org/10.1073/pnas.1117208109 CrossRefPubMedPubMedCentralGoogle Scholar
  52. 52.
    Lanitis E, Smith JB, Dangaj D, Flingai S, Poussin M, Xu S, Czerniecki BJ, Li YF, Robbins PF, Powell DJ Jr (2014) A human ErbB2-specific T-cell receptor confers potent antitumor effector functions in genetically engineered primary cytotoxic lymphocytes. Hum Gene Ther 25(8):730–739.  https://doi.org/10.1089/hum.2014.006 CrossRefPubMedPubMedCentralGoogle Scholar
  53. 53.
    Kershaw MH, Westwood JA, Parker LL, Wang G, Eshhar Z, Mavroukakis SA, White DE, Wunderlich JR, Canevari S, Rogers-Freezer L, Chen CC, Yang JC, Rosenberg SA, Hwu P (2006) A phase I study on adoptive immunotherapy using gene-modified T cells for ovarian cancer. Clin Cancer Res 12(20 Pt 1):6106–6115.  https://doi.org/10.1158/1078-0432.CCR-06-1183 CrossRefPubMedPubMedCentralGoogle Scholar
  54. 54.
    Alexandrov LB, Nik-Zainal S, Wedge DC, Aparicio SA, Behjati S, Biankin AV, Bignell GR, Bolli N, Borg A, Borresen-Dale AL, Boyault S, Burkhardt B, Butler AP, Caldas C, Davies HR, Desmedt C, Eils R, Eyfjord JE, Foekens JA, Greaves M, Hosoda F, Hutter B, Ilicic T, Imbeaud S, Imielinski M, Jager N, Jones DT, Jones D, Knappskog S, Kool M, Lakhani SR, Lopez-Otin C, Martin S, Munshi NC, Nakamura H, Northcott PA, Pajic M, Papaemmanuil E, Paradiso A, Pearson JV, Puente XS, Raine K, Ramakrishna M, Richardson AL, Richter J, Rosenstiel P, Schlesner M, Schumacher TN, Span PN, Teague JW, Totoki Y, Tutt AN, Valdes-Mas R, van Buuren MM, van’t Veer L, Vincent-Salomon A, Waddell N, Yates LR, Australian Pancreatic Cancer Genome I, Consortium IBC, Consortium IM-S, PedBrain I, Zucman-Rossi J, Futreal PA, McDermott U, Lichter P, Meyerson M, Grimmond SM, Siebert R, Campo E, Shibata T, Pfister SM, Campbell PJ, Stratton MR (2013) Signatures of mutational processes in human cancer. Nature 500(7463):415–421.  https://doi.org/10.1038/nature12477 CrossRefPubMedPubMedCentralGoogle Scholar
  55. 55.
    Martin SD, Brown SD, Wick DA, Nielsen JS, Kroeger DR, Twumasi-Boateng K, Holt RA, Nelson BH (2016) Low mutation burden in ovarian cancer may limit the utility of neoantigen-targeted vaccines. PLoS One 11(5):e0155189.  https://doi.org/10.1371/journal.pone.0155189 CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  • Donastas Sakellariou-Thompson
    • 1
  • Marie-Andrée Forget
    • 1
  • Emily Hinchcliff
    • 2
  • Joseph Celestino
    • 2
  • Patrick Hwu
    • 1
  • Amir A. Jazaeri
    • 2
  • Cara Haymaker
    • 3
    Email author
  • Chantale Bernatchez
    • 1
    • 3
    Email author
  1. 1.Department of Melanoma Medical OncologyThe University of Texas MD Anderson Cancer Center (UT MDACC)HoustonUSA
  2. 2.Department of Gynecologic Oncology and Reproductive MedicineUTMDACCHoustonUSA
  3. 3.Department of Translational Molecular PathologyUT MDACCHoustonUSA

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