Annals of Surgical Oncology

, Volume 25, Issue 11, pp 3404–3412 | Cite as

An Update on Immunotherapy for Solid Tumors: A Review

  • Toan PhamEmail author
  • Sara Roth
  • Joseph Kong
  • Glen Guerra
  • Vignesh Narasimhan
  • Lloyd Pereira
  • Jayesh Desai
  • Alexander Heriot
  • Robert Ramsay
Translational Research and Biomarkers


In recent years, it has been demonstrated that immunotherapy is an effective strategy for the management of solid tumors. The origins of immunotherapy can be traced back to the work of William Coley, who elicited an immune response against sarcoma by injecting patients with a mixture of dead bacteria. Significant progress has been made since, with immune markers within the tumor now being used as predictors of cancer prognosis and manipulated to improve patient survival. While surgery remains central to the management of most patients with solid malignancies, it is important that surgeons consider the different immunotherapy strategies that can be employed to manage disease. Here, we highlight how the immune system influences tumorigenesis and bring attention to how current and future immunotherapies can serve as an adjunct to surgery.



Not applicable.


All authors are involved in the MYPHISMO clinical trial (NCT03287427).


  1. 1.
    World Health Organization Cancer Factsheet. 2018; Accessed 18 Feb 2018.
  2. 2.
    Weber JS, O’Day S, Urba W, et al. Phase I/II study of ipilimumab for patients with metastatic melanoma. J Clin Oncol. 2008;26(36):5950–56.PubMedCrossRefGoogle Scholar
  3. 3.
    Coley WB. The treatment of inoperable sarcoma by bacterial toxins (the mixed toxins of the Streptococcus erysipelas and the Bacillus prodigiosus). Proc R Soc Med. 1910;3:1–48.PubMedPubMedCentralGoogle Scholar
  4. 4.
    Coley WB. The treatment of malignant tumors by repeated inoculations of erysipelas. With a report of ten original cases. 1893. Clin Orthop Relat Res. 1991(262):3–11.Google Scholar
  5. 5.
    Wolchok JD, Chiarion-Sileni V, Gonzalez R, et al. Overall survival with combined nivolumab and ipilimumab in advanced melanoma. N Engl J Med. 2017;377(14):1345–56.Google Scholar
  6. 6.
    Ott PA, Hodi FS, Kaufman HL, Wigginton JM, Wolchok JD. Combination immunotherapy: a road map. J Immunother Cancer. 2017;5:16.PubMedPubMedCentralCrossRefGoogle Scholar
  7. 7.
    Dunn GP, Bruce AT, Ikeda H, Old LJ, Schreiber RD. Cancer immunoediting: from immunosurveillance to tumor escape. Nat Immunol. 2002;3(11):991–8.PubMedCrossRefGoogle Scholar
  8. 8.
    Galon J, Costes A, Sanchez-Cabo F, et al. Type, density, and location of immune cells within human colorectal tumors predict clinical outcome. Science. 2006;313(5795):1960–4.PubMedCrossRefGoogle Scholar
  9. 9.
    Mlecnik B, Tosolini M, Kirilovsky A, et al. Histopathologic-based prognostic factors of colorectal cancers are associated with the state of the local immune reaction. J Clin Oncol. 2011;29(6):610–8.PubMedCrossRefGoogle Scholar
  10. 10.
    Galon J, Mlecnik B, Bindea G, et al. Towards the introduction of the ‘Immunoscore’ in the classification of malignant tumours. J Pathol. 2014;232:199–209.PubMedCrossRefPubMedCentralGoogle Scholar
  11. 11.
    Galon J, Mlecnik B, Marliot F, et al. Validation of the Immunoscore (IM) as a prognostic marker in stage I/II/III colon cancer: Results of a worldwide consortium-based analysis of 1,336 patients. J Clin Oncol. 2016;34(15):3500–3500.Google Scholar
  12. 12.
    Pages F, Mlecnik B, Marliot F, et al. International validation of the consensus Immunoscore for the classification of colon cancer: a prognostic and accuracy study. Lancet. 2018;391(10135):2128–39.PubMedCrossRefPubMedCentralGoogle Scholar
  13. 13.
    Fujitani K, Ando M, Sakamaki K, et al. A prospective multicenter observational study of surgical palliation examining postoperative quality of life in patients treated for malignant gastric outlet obstruction caused by incurable advanced gastric cancer. J Clin Oncol. 2017;35(4):6-6.Google Scholar
  14. 14.
    Qi X, Jiang Y, Zhang Q, et al. Prognostic and predictive value of immunoscore signature in gastric cancer. J Clin Oncol. 2017;35(15):e15594-e15594.CrossRefGoogle Scholar
  15. 15.
    Galon J, Fox BA, Bifulco CB, et al. Immunoscore and immunoprofiling in cancer: an update from the melanoma and immunotherapy bridge 2015. J Transl Med. 2016;14(1):273.PubMedPubMedCentralCrossRefGoogle Scholar
  16. 16.
    Pilch YH, Myers GH, Sparks FC, Golub SH. Prospects for the immunotherapy of cancer. Part I: basic concepts of tumor immunologyProspects for the immunotherapy of cancer. Part I: basic concepts of tumor immunology. Curr Probl Surg. 1975;12(1):1–46.CrossRefGoogle Scholar
  17. 17.
    Dunn GP, Old LJ, Schreiber RD. The three Es of cancer immunoediting. Annu Rev Immunol. 2004;22:329–60.PubMedCrossRefPubMedCentralGoogle Scholar
  18. 18.
    Lipson EJ, Drake CG. Ipilimumab: an anti-CTLA-4 antibody for metastatic melanoma. Clin Cancer Res. 2011;17(22):6958–62.PubMedPubMedCentralCrossRefGoogle Scholar
  19. 19.
    Hodi FS, O’Day SJ, McDermott DF, et al. Improved survival with ipilimumab in patients with metastatic melanoma. N Engl J Med. 19 2010;363(8):711–23.PubMedPubMedCentralCrossRefGoogle Scholar
  20. 20.
    Ribas A. Tumor immunotherapy directed at PD-1. N Engl J Med. 2012;366(26):2517–9.PubMedCrossRefPubMedCentralGoogle Scholar
  21. 21.
    Robert C, Schachter J, Long GV, et al. Pembrolizumab versus ipilimumab in advanced melanoma. N Engl J Med. 2015;372(26):2521–32.PubMedCrossRefPubMedCentralGoogle Scholar
  22. 22.
    Ribas A, Puzanov I, Dummer R, et al. Pembrolizumab versus investigator-choice chemotherapy for ipilimumab-refractory melanoma (KEYNOTE-002): a randomised, controlled, phase 2 trial. Lancet Oncol. 2015;16(8):908–18.PubMedCrossRefPubMedCentralGoogle Scholar
  23. 23.
    Herbst RS, Baas P, Kim DW, et al. Pembrolizumab versus docetaxel for previously treated, PD-L1-positive, advanced non-small-cell lung cancer (KEYNOTE-010): a randomised controlled trial. Lancet. 2016;387(10027):1540–50.PubMedCrossRefGoogle Scholar
  24. 24.
    Le DT, Uram JN, Wang H, et al. PD-1 Blockade in tumors with mismatch-repair deficiency. N Engl J Med. 2015;372(26):2509–20.PubMedPubMedCentralCrossRefGoogle Scholar
  25. 25.
    Fuchs CS, Doi T, Jang RW-J, et al. KEYNOTE-059 cohort 1: Efficacy and safety of pembrolizumab (pembro) monotherapy in patients with previously treated advanced gastric cancer. J Clin Oncol. 2017;35(15):4003-4003.Google Scholar
  26. 26.
    Ribas A, Hodi FS, Lawrence D, et al. 1216OKEYNOTE-022 update: phase 1 study of first-line pembrolizumab (pembro) plus dabrafenib (D) and trametinib (T) for BRAF-mutant advanced melanoma. Vol 282017.Google Scholar
  27. 27.
    Dudley ME, Wunderlich J, Nishimura MI, et al. Adoptive transfer of cloned melanoma-reactive T lymphocytes for the treatment of patients with metastatic melanoma. J Immunother. 2001;24(4):363–73.CrossRefGoogle Scholar
  28. 28.
    Dudley ME, Wunderlich JR, Yang JC, et al. A phase I study of nonmyeloablative chemotherapy and adoptive transfer of autologous tumor antigen-specific T lymphocytes in patients with metastatic melanoma. J Immunother. 2002;25(3):243–51.CrossRefGoogle Scholar
  29. 29.
    Zhou P, Tian S, Li J, et al. Paradoxes in thyroid carcinoma treatment: analysis of the SEER database 2010–2013. Oncotarget. 2017;8(1):345–53.PubMedGoogle Scholar
  30. 30.
    Ostrom QT, Gittleman H, Kruchko C, et al. Completeness of required site-specific factors for brain and CNS tumors in the Surveillance, Epidemiology and End Results (SEER) 18 database (2004–2012, varying). J Neurooncol. 2016;130(1):31–42.PubMedPubMedCentralCrossRefGoogle Scholar
  31. 31.
    Liao Z, Rodrigues MC, Poynter JN, Amatruda JF, Rodriguez-Galindo C, Frazier AL. Risk of second malignant neoplasms in women and girls with germ cell tumors. Ann Oncol. 2017;28(2):329–32.PubMedGoogle Scholar
  32. 32.
    Yao N, Alcala HE, Anderson R, Balkrishnan R. Cancer disparities in rural Appalachia: incidence, early detection, and survivorship. J Rural Health. 2017;33(4):375–81.PubMedCrossRefGoogle Scholar
  33. 33.
    Shah BK, Kandel P, Khanal A. Second primary malignancies in hepatocellular cancer - A US population-based study. Anticancer Res. 2016;36(7):3511–4.PubMedGoogle Scholar
  34. 34.
    Deniger DC, Kwong ML, Pasetto A, et al. A pilot trial of the combination of vemurafenib with adoptive cell therapy in patients with metastatic melanoma. Clin Cancer Res. 2017;23(2):351–62.PubMedCrossRefGoogle Scholar
  35. 35.
    Bista A, Sharma S, Shah BK. Disparities in receipt of radiotherapy and survival by age, sex, and ethnicity among patient with stage I follicular lymphoma. Front Oncol. 2016;6:101.PubMedPubMedCentralCrossRefGoogle Scholar
  36. 36.
    Crompton JG, Klemen N, Kammula US. Metastasectomy for tumor-infiltrating lymphocytes: an emerging operative indication in surgical oncology. Ann Surg Oncol. 2018;25(2):565–72.CrossRefGoogle Scholar
  37. 37.
    Reits EA, Hodge JW, Herberts CA, et al. Radiation modulates the peptide repertoire, enhances MHC class I expression, and induces successful antitumor immunotherapy. J Exp Med. 2006;203(5):1259–71.PubMedPubMedCentralCrossRefGoogle Scholar
  38. 38.
    Haikerwal SJ, Hagekyriakou J, MacManus M, Martin OA, Haynes NM. Building immunity to cancer with radiation therapy. Cancer Lett. 2015;368(2):198–208.PubMedCrossRefGoogle Scholar
  39. 39.
    Reynders K, Illidge T, Siva S, Chang JY, De Ruysscher D. The abscopal effect of local radiotherapy: using immunotherapy to make a rare event clinically relevant. Cancer Treat Rev. 2015;41(6):503–10.PubMedPubMedCentralCrossRefGoogle Scholar
  40. 40.
    Ko EC, Formenti SC. Radiotherapy and checkpoint inhibitors: a winning new combination? Ther Adv Med Oncol. 2018;10:1758835918768240.PubMedPubMedCentralCrossRefGoogle Scholar
  41. 41.
    Dovedi SJ, Illidge TM. The antitumor immune response generated by fractionated radiation therapy may be limited by tumor cell adaptive resistance and can be circumvented by PD-L1 blockade. Oncoimmunology. 2015;4(7):e1016709.PubMedPubMedCentralCrossRefGoogle Scholar
  42. 42.
    Lawler SE, Speranza MC, Cho CF, Chiocca EA. Oncolytic viruses in cancer treatment: a review. JAMA Oncol. 2017;3(6):841–9.PubMedCrossRefPubMedCentralGoogle Scholar
  43. 43.
    Fukuhara H, Ino Y, Todo T. Oncolytic virus therapy: A new era of cancer treatment at dawn. Cancer Sci. 2016;107(10):1373–9.PubMedPubMedCentralCrossRefGoogle Scholar
  44. 44.
    Kaufman HL, Bines SD. OPTIM trial: a Phase III trial of an oncolytic herpes virus encoding GM-CSF for unresectable stage III or IV melanoma. Future Oncol. Jun 2010;6(6):941–9.PubMedCrossRefPubMedCentralGoogle Scholar
  45. 45.
    Breitbach CJ, Moon A, Burke J, Hwang TH, Kirn DH. A phase 2, open-label, randomized study of Pexa-Vec (JX-594) administered by intratumoral injection in patients with unresectable primary hepatocellular carcinoma. Methods Mol Biol. 2015;1317:343–57.PubMedCrossRefGoogle Scholar
  46. 46.
    Dalgleish AG, Whelan MA. Cancer vaccines as a therapeutic modality: The long trek. Cancer Immunol Immunother. 2006;55(8):1025–32.PubMedCrossRefGoogle Scholar
  47. 47.
    Ott PA, Hu Z, Keskin DB, et al. An immunogenic personal neoantigen vaccine for patients with melanoma. Nature. 2017;547(7662):217–21.PubMedPubMedCentralCrossRefGoogle Scholar
  48. 48.
    Sahin U, Derhovanessian E, Miller M, et al. Personalized RNA mutanome vaccines mobilize poly-specific therapeutic immunity against cancer. Nature. 2017;547(7662):222–6.PubMedCrossRefGoogle Scholar
  49. 49.
    Kantoff PW, Higano CS, Shore ND, et al. Sipuleucel-T immunotherapy for castration-resistant prostate cancer. N Engl J Med. 2010;363(5):411–22.PubMedCrossRefGoogle Scholar
  50. 50.
    Weden S, Klemp M, Gladhaug IP, et al. Long-term follow-up of patients with resected pancreatic cancer following vaccination against mutant K-ras. Int J Cancer. 2011;128(5):1120–8.PubMedCrossRefGoogle Scholar
  51. 51.
    MYPHISMO: MYB and PD-1 Immunotherapies against multiple oncologies trial.
  52. 52.
    Garrido F, Perea F, Bernal M, Sanchez-Palencia A, Aptsiauri N, Ruiz-Cabello F. The escape of cancer from T cell-mediated immune surveillance: HLA class I loss and tumor tissue architecture. Vaccines (Basel). 2017;5(1):7.PubMedCentralCrossRefGoogle Scholar
  53. 53.
    Garrido F, Ruiz-Cabello F, Aptsiauri N. Rejection versus escape: the tumor MHC dilemma. Cancer Immunol Immunother. 2017;66(2):259–71.PubMedCrossRefPubMedCentralGoogle Scholar
  54. 54.
    Zaretsky JM, Garcia-Diaz A, Shin DS, et al. Mutations associated with acquired resistance to PD-1 blockade in melanoma. N Engl J Med. 2016;375(9):819–29.PubMedPubMedCentralCrossRefGoogle Scholar
  55. 55.
    Tonn T, Schwabe D, Klingemann HG, et al. Treatment of patients with advanced cancer with the natural killer cell line NK-92. Cytotherapy. 2013;15(12):1563–70.PubMedCrossRefPubMedCentralGoogle Scholar
  56. 56.
    Yang YJ, Park JC, Kim HK, Kang JH, Park SY. A trial of autologous ex vivo-expanded NK cell-enriched lymphocytes with docetaxel in patients with advanced non-small cell lung cancer as second- or third-line treatment: phase IIa study. Anticancer Res. 2013;33(5):2115–22.PubMedPubMedCentralGoogle Scholar
  57. 57.
    Sakamoto N, Ishikawa T, Kokura S, et al. Phase I clinical trial of autologous NK cell therapy using novel expansion method in patients with advanced digestive cancer. J Transl Med. 2015;13:277.PubMedPubMedCentralCrossRefGoogle Scholar
  58. 58.
    Geller MA, Cooley S, Judson PL, et al. A phase II study of allogeneic natural killer cell therapy to treat patients with recurrent ovarian and breast cancer. Cytotherapy. 2011;13(1):98–107.PubMedCrossRefPubMedCentralGoogle Scholar
  59. 59.
    Arai S, Meagher R, Swearingen M, et al. Infusion of the allogeneic cell line NK-92 in patients with advanced renal cell cancer or melanoma: a phase I trial. Cytotherapy. 2008;10(6):625–32.PubMedCrossRefPubMedCentralGoogle Scholar
  60. 60.
    Ammam M. Immunotherapy based on natural killer cells may soon begin clinical studies. In: M. Nace (Ed) Immuno-Oncology News. Dallas, TX: BioNews Services, LLC; 2017.Google Scholar
  61. 61.
    Rezvani K, Rouce R, Liu E, Shpall E. Engineering natural killer cells for cancer immunotherapy. Mol Ther. 2017;25(8):1769–81.PubMedPubMedCentralCrossRefGoogle Scholar
  62. 62.
    Porter DL, Kalos M, Zheng Z, Levine B, June C. Chimeric antigen receptor therapy for B-cell malignancies. J Cancer. 2011;2:331–2.PubMedPubMedCentralCrossRefGoogle Scholar
  63. 63.
    Porter DL, Hwang WT, Frey NV, et al. Chimeric antigen receptor T cells persist and induce sustained remissions in relapsed refractory chronic lymphocytic leukemia. Sci Transl Med. 2015;7(303):303ra139.PubMedPubMedCentralCrossRefGoogle Scholar
  64. 64.
    FDA US. FDA approval brings first gene therapy to the United States. CAR T-cell therapy approved to treat certain children and young adults with B-cell acute lymphoblastic leukemia: FDA, USA; 2017.Google Scholar
  65. 65.
    Yu S, Li A, Liu Q, et al. Chimeric antigen receptor T cells: a novel therapy for solid tumors. J Hematol Oncol. 2017;10(1):78.PubMedPubMedCentralCrossRefGoogle Scholar
  66. 66.
    Feng K, Guo Y, Dai H, et al. Chimeric antigen receptor-modified T cells for the immunotherapy of patients with EGFR-expressing advanced relapsed/refractory non-small cell lung cancer. Sci China Life Sci. 2016;59(5):468–79.PubMedCrossRefPubMedCentralGoogle Scholar
  67. 67.
    A phase I trial of T cells expressing an anti-GD2 chimeric antigen receptor in children and young adults with GD2+ solid tumors.
  68. 68.
    CMV-specific cytotoxic T lymphocytes expressing CAR targeting HER2 in patients with gbm.
  69. 69.
    Pilot study of autologous anti-EGFRvIII CAR T cells in recurrent glioblastoma multiforme.
  70. 70.
    Kawalec P, Paszulewicz A, Holko P, Pilc A. Sipuleucel-T immunotherapy for castration-resistant prostate cancer. A systematic review and meta-analysis. Arch Med Sci. 2012;8(5):767–75.PubMedPubMedCentralCrossRefGoogle Scholar
  71. 71.
    A study of mesothelin redirected autologous T cells for advanced pancreatic carcinoma.
  72. 72.
    Pilot study of autologous T-cells in patients with metastatic pancreatic cancer.
  73. 73.
    Katz SC, Burga RA, McCormack E, et al. Phase I hepatic immunotherapy for metastases study of intra-arterial chimeric antigen receptor-modified T-cell therapy for CEA+ liver metastases. Clin Cancer Res. 2015;21(14):3149–59.PubMedPubMedCentralCrossRefGoogle Scholar
  74. 74.
    Ahmed N, Brawley VS, Hegde M, et al. Human epidermal growth factor receptor 2 (HER2)-specific chimeric antigen receptor-modified T cells for the immunotherapy of HER2-positive sarcoma. J Clin Oncol. 2015;33(15):1688–96.PubMedPubMedCentralCrossRefGoogle Scholar
  75. 75.
    Her2 chimeric antigen receptor expressing T cells in advanced sarcoma.
  76. 76.
    Hegde UP, Mukherji B. Current status of chimeric antigen receptor engineered T cell-based and immune checkpoint blockade-based cancer immunotherapies. Cancer Immunol Immunother. 2017;66(9):1113–21.PubMedPubMedCentralCrossRefGoogle Scholar
  77. 77.
    Lindau D, Gielen P, Kroesen M, Wesseling P, Adema GJ. The immunosuppressive tumour network: myeloid-derived suppressor cells, regulatory T cells and natural killer T cells. Immunology. 2013;138(2):105–15.PubMedPubMedCentralCrossRefGoogle Scholar
  78. 78.
    Tanaka A, Sakaguchi S. Regulatory T cells in cancer immunotherapy. Cell Res. 2017;27(1):109–18.PubMedCrossRefGoogle Scholar
  79. 79.
    Liu C, Workman CJ, Vignali DA. Targeting regulatory T cells in tumors. FEBS J. 2016;283(14):2731–48.PubMedCrossRefGoogle Scholar
  80. 80.
    Rech AJ, Vonderheide RH. Clinical use of anti-CD25 antibody daclizumab to enhance immune responses to tumor antigen vaccination by targeting regulatory T cells. Ann N Y Acad Sci. 2009;1174:99–106.PubMedCrossRefPubMedCentralGoogle Scholar
  81. 81.
    Rech AJ, Mick R, Martin S, et al. CD25 blockade depletes and selectively reprograms regulatory T cells in concert with immunotherapy in cancer patients. Sci Transl Med. 2012;4(134):134–62.CrossRefGoogle Scholar
  82. 82.
    Telang S, Rasku MA, Clem AL, et al. Phase II trial of the regulatory T cell-depleting agent, denileukin diftitox, in patients with unresectable stage IV melanoma. BMC Cancer. 2011;11:515.PubMedPubMedCentralCrossRefGoogle Scholar
  83. 83.
    Romano E, Kusio-Kobialka M, Foukas PG, et al. Ipilimumab-dependent cell-mediated cytotoxicity of regulatory T cells ex vivo by nonclassical monocytes in melanoma patients. Proc Natl Acad Sci U S A. 2015;112(19):6140–5.PubMedPubMedCentralCrossRefGoogle Scholar
  84. 84.
    Tobin RP, Davis D, Jordan KR, McCarter MD. The clinical evidence for targeting human myeloid-derived suppressor cells in cancer patients. J Leukoc Biol. 2017;102(2):381–91.PubMedCrossRefPubMedCentralGoogle Scholar
  85. 85.
    Schilling B, Sucker A, Griewank K, et al. Vemurafenib reverses immunosuppression by myeloid derived suppressor cells. Int J Cancer. 2013;133(7):1653–63.PubMedCrossRefPubMedCentralGoogle Scholar
  86. 86.
    de Coana YP, Wolodarski M, Poschke I, et al. Ipilimumab treatment decreases monocytic MDSCs and increases CD8 effector memory T cells in long-term survivors with advanced melanoma. Oncotarget. 2017;8(13):21539–53.PubMedPubMedCentralCrossRefGoogle Scholar
  87. 87.
    Ko JS, Rayman P, Ireland J, et al. Direct and differential suppression of myeloid-derived suppressor cell subsets by sunitinib is compartmentally constrained. Cancer Res. 2010;70(9):3526–36.PubMedPubMedCentralCrossRefGoogle Scholar
  88. 88.
    Mirza N, Fishman M, Fricke I, et al. All-trans-retinoic acid improves differentiation of myeloid cells and immune response in cancer patients. Cancer Res. 2006;66(18):9299–307.PubMedPubMedCentralCrossRefGoogle Scholar
  89. 89.
    Lathers DM, Clark JI, Achille NJ, Young MR. Phase 1B study to improve immune responses in head and neck cancer patients using escalating doses of 25-hydroxyvitamin D3. Cancer Immunol Immunother. 2004;53(5):422–30.PubMedCrossRefPubMedCentralGoogle Scholar
  90. 90.
    Noonan KA, Ghosh N, Rudraraju L, Bui M, Borrello I. Targeting immune suppression with PDE5 inhibition in end-stage multiple myeloma. Cancer Immunol Res. 2014;2(8):725–31.PubMedPubMedCentralCrossRefGoogle Scholar
  91. 91.
    Weed DT, Vella JL, Reis IM, et al. Tadalafil reduces myeloid-derived suppressor cells and regulatory T cells and promotes tumor immunity in patients with head and neck squamous cell carcinoma. Clin Cancer Res. 2015;21(1):39–48.PubMedCrossRefGoogle Scholar
  92. 92.
    Annels NE, Shaw VE, Gabitass RF, et al. The effects of gemcitabine and capecitabine combination chemotherapy and of low-dose adjuvant GM-CSF on the levels of myeloid-derived suppressor cells in patients with advanced pancreatic cancer. Cancer Immunol Immunother. 2014;63(2):175–83.PubMedCrossRefGoogle Scholar
  93. 93.
    Kanterman J, Sade-Feldman M, Biton M, et al. Adverse immunoregulatory effects of 5FU and CPT11 chemotherapy on myeloid-derived suppressor cells and colorectal cancer outcomes. Cancer Res. 2014;74(21):6022–35.PubMedCrossRefGoogle Scholar
  94. 94.
    Fischer K, Hoffmann P, Voelkl S, et al. Inhibitory effect of tumor cell-derived lactic acid on human T cells. Blood. 2007;109(9):3812–9.PubMedCrossRefGoogle Scholar
  95. 95.
    Chang CH, Qiu J, O’Sullivan D, et al. Metabolic competition in the tumor microenvironment is a driver of cancer progression. Cell. 2015;162(6):1229–41.PubMedPubMedCentralCrossRefGoogle Scholar
  96. 96.
    Allavena P, Germano G, Marchesi F, Mantovani A. Chemokines in cancer related inflammation. Exp Cell Res. 2011;317(5):664–73.PubMedCrossRefPubMedCentralGoogle Scholar
  97. 97.
    Griffioen AW, Damen CA, Martinotti S, Blijham GH, Groenewegen G. Endothelial intercellular adhesion molecule-1 expression is suppressed in human malignancies: the role of angiogenic factors. Cancer Res. 1996;56(5):1111–7.PubMedPubMedCentralGoogle Scholar
  98. 98.
    Lider O, Mekori YA, Miller T, et al. Inhibition of T lymphocyte heparanase by heparin prevents T cell migration and T cell-mediated immunity. Eur J Immunol. 1990;20(3):493–9.PubMedCrossRefPubMedCentralGoogle Scholar
  99. 99.
    Kalluri R, Zeisberg M. Fibroblasts in cancer. Nat Rev Cancer. 2006;6(5):392–401.PubMedCrossRefPubMedCentralGoogle Scholar
  100. 100.
    Shin HC, Han W, Moon HG, et al. Breast-conserving surgery after tumor downstaging by neoadjuvant chemotherapy is oncologically safe for stage III breast cancer patients. Ann Surg Oncol. 2013;20(8):2582–9.PubMedCrossRefPubMedCentralGoogle Scholar
  101. 101.
    Vuky J, Corman JM, Porter C, Olgac S, Auerbach E, Dahl K. Phase II trial of neoadjuvant docetaxel and CG1940/CG8711 followed by radical prostatectomy in patients with high-risk clinically localized prostate cancer. Oncologist. 2013;18(6):687–8.PubMedPubMedCentralCrossRefGoogle Scholar
  102. 102.
    Long GV, Weber JS, Larkin J, et al. Nivolumab for patients with advanced melanoma treated beyond progression: analysis of 2 phase 3 clinical trials. JAMA Oncol. 2017;3(11):1511–19.PubMedPubMedCentralCrossRefGoogle Scholar

Copyright information

© Society of Surgical Oncology 2018

Authors and Affiliations

  • Toan Pham
    • 1
    • 2
    • 3
    • 4
    Email author
  • Sara Roth
    • 1
  • Joseph Kong
    • 1
    • 2
    • 3
    • 4
  • Glen Guerra
    • 1
    • 2
    • 3
    • 4
  • Vignesh Narasimhan
    • 1
    • 2
    • 3
    • 4
  • Lloyd Pereira
    • 1
  • Jayesh Desai
    • 3
  • Alexander Heriot
    • 1
    • 2
    • 3
    • 4
  • Robert Ramsay
    • 1
    • 5
  1. 1.Divisions of Cancer ResearchPeter MacCallum Cancer CentreMelbourneAustralia
  2. 2.Cancer SurgeryMelbourneAustralia
  3. 3.Sir Peter MacCallum Department of OncologyUniversity of MelbourneMelbourneAustralia
  4. 4.Department of SurgeryUniversity of MelbourneMelbourneAustralia
  5. 5.Department of PathologyUniversity of MelbourneMelbourneAustralia

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