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Immunological Treatment in Gastrointestinal Cancers

  • Héctor Randhall Callata-Carhuapoma
  • Jesús García-Foncillas LópezEmail author
Chapter

Abstract

Colorectal cancer is a common malignancy around the world, with an important mortality rate among other malignancies. The cornerstone of treatment is curative surgery as 40% of patients are diagnosed with localized disease. Patients who were diagnosed with advanced disease have a dismal prognosis. Conventional chemotherapy is the standard treatment in an advanced setting with important development of strategies that combine biological agents (bevacizumab, cetuximab, panitumumab, ramucirumab, etc.). Recently the better understanding of immune system interaction in carcinogenesis has led to the development of new therapeutic strategies based on immune modulators that activate the immune system. With the current evidence we have, probably a combination of these strategies will result in better outcomes in the fight against this malignancy.

Keywords

Colorectal cancer  Immune system  Vaccines  Cytokines Adoptive cell therapy  Checkpoint inhibitors  Anti-PD-1  Anti-CTLA-4  Combination therapy 

References

  1. 1.
    Bray F, Ren JS, Masuyer E FJ. GLOBOCAN 2012 v1.0. International Agency for Research on Cancer, World Health Organization, Lyon, France; 2013. http://globocan.iarc.fr/Default.aspx Accessed 18 Mar 2016.
  2. 2.
    Las Cifras del Cáncer en España en 2016. Accessed 18 Mar 2016. http://seom.org/seomcms/images/stories/recursos/LA_CIFRAS_DEL_CANCER_EN_2016.pdf.
  3. 3.
    American Cancer Society. Colorectal cancer facts & figures 2014–2016. Atlanta: American Cancer Society. 2014. Accessed 18 Mar 2016. http://www.cancer.org/acs/groups/content/documents/document/acspc-042280.pdf.
  4. 4.
    Hellinger MD, Santiago CA. Reoperation for recurrent colorectal cancer. Clin Colon Rectal Surg. 2006;19(4):228–36.CrossRefPubMedPubMedCentralGoogle Scholar
  5. 5.
    Kocián P, Šedivcová M, Drgáč J, Cerná K, Hoch J, Kodet R, et al. Tumor-infiltrating lymphocytes and dendritic cells in human colorectal cancer: their relationship to KRAS mutational status and disease recurrence. Hum Immunol. 2011;72(11):1022–8.CrossRefPubMedGoogle Scholar
  6. 6.
    Gonzalez-Pons M, Cruz-Correa M. Colorectal cancer biomarkers: where are we now? Biomed Res Int. 2015;2015:149014.CrossRefPubMedPubMedCentralGoogle Scholar
  7. 7.
    Deschoolmeester V, Baay M, Specenier P, Lardon F, Vermorken JB. A review of the most promising biomarkers in colorectal cancer: one step closer to targeted therapy. Oncologist AlphaMed Press. 2010;15(7):699–731.CrossRefGoogle Scholar
  8. 8.
    Pernot S, Terme M, Voron T, Colussi O, Marcheteau E, Tartour E, et al. Colorectal cancer and immunity: what we know and perspectives. World J Gastroenterol. 2014;20(14):3738–50.CrossRefPubMedPubMedCentralGoogle Scholar
  9. 9.
    Frisch M. Association of cancer with AIDS-related immunosuppression in adults. JAMA. 2001;285(13):1736–45.CrossRefPubMedGoogle Scholar
  10. 10.
    Shankaran V, Ikeda H, Bruce AT, White JM, Swanson PE, Old LJ, et al. IFNgamma and lymphocytes prevent primary tumour development and shape tumour immunogenicity. Nature. 2001;410(6832):1107–11.CrossRefPubMedGoogle Scholar
  11. 11.
    Dunn GP, Bruce AT, Ikeda H, Old LJ, Schreiber RD. Cancer immunoediting: from immunosurveillance to tumor escape. Nat Immunol. 2002;3(11):991–8.CrossRefGoogle Scholar
  12. 12.
    Markman JL, Shiao SL. Impact of the immune system and immunotherapy in colorectal cancer. J Gastrointest Oncol. 2015;6(1):208–23.PubMedPubMedCentralGoogle Scholar
  13. 13.
    Malmberg K-J, Bryceson YT, Carlsten M, Andersson S, Björklund A, Björkström NK, et al. NK cell-mediated targeting of human cancer and possibilities for new means of immunotherapy. Cancer Immunol Immunother. 2008;57(10):1541–52.CrossRefPubMedGoogle Scholar
  14. 14.
    Carbone E, Neri P, Mesuraca M, Fulciniti MT, Otsuki T, Pende D, et al. HLA class I, NKG2D, and natural cytotoxicity receptors regulate multiple myeloma cell recognition by natural killer cells. Blood Am Soc Hematol. 2005;105(1):251–8.Google Scholar
  15. 15.
    Terme M, Fridman WH, Tartour E. NK cells from pleural effusions are potent antitumor effector cells. Eur J Immunol. 2013;43(2):331–4.CrossRefPubMedGoogle Scholar
  16. 16.
    Coca S, Perez-Piqueras J, Martinez D, Colmenarejo a SM a, Vallejo C, et al. The prognostic significance of intratumoral natural killer cells in patients with colorectal carcinoma. Cancer. 1997;79(12):2320–8.CrossRefGoogle Scholar
  17. 17.
    Tachibana T, Onodera H, Tsuruyama T, Mori A, Nagayama S, Hiai H, et al. Increased intratumor Valpha24-positive natural killer T cells: a prognostic factor for primary colorectal carcinomas. Clin Cancer Res. 2005;11(20):7322–7.CrossRefPubMedGoogle Scholar
  18. 18.
    Pollard JW. Tumour-educated macrophages promote tumour progression and metastasis. Nat Rev Cancer. 2004;4(1):71–8.CrossRefPubMedGoogle Scholar
  19. 19.
    Edin S, Wikberg ML, Rutegård J, Oldenborg P-A, Palmqvist R. Phenotypic skewing of macrophages in vitro by secreted factors from colorectal cancer cells. PLoS One. 2013;8(9):e74982.CrossRefPubMedPubMedCentralGoogle Scholar
  20. 20.
    Erreni M, Mantovani A, Allavena P. Tumor-associated macrophages (TAM) and inflammation in colorectal cancer. Cancer Microenviron. 2011;4(2):141–54.CrossRefPubMedGoogle Scholar
  21. 21.
    Jacobs J, Smits E, Lardon F, Pauwels P, Deschoolmeester V. Immune checkpoint modulation in colorectal cancer: what’s new and what to expect. J Immunol Res. 2015;2015:158038.CrossRefPubMedPubMedCentralGoogle Scholar
  22. 22.
    Golubovskaya V, Wu L. Different subsets of T cells, memory, effector functions, and CAR-T immunotherapy. Cancers (Basel). 8(3).CrossRefPubMedCentralGoogle Scholar
  23. 23.
    Obermajer N, Dahlke MH. (Compl)Ex-Th17-Treg cell inter-relationship. Oncoimmunology. 2015;5(1):e1040217.CrossRefPubMedPubMedCentralGoogle Scholar
  24. 24.
    Yao Y, Jiang Q, Jiang L, Wu J, Zhang Q, Wang J, et al. Lnc-SGK1 induced by Helicobacter pylori infection and highsalt diet promote Th2 and Th17 differentiation in human gastric cancer by SGK1/Jun B signaling. Oncotarget. 2016;7(15):20549–60.CrossRefPubMedPubMedCentralGoogle Scholar
  25. 25.
    Amin M, Lockhart AC. The potential role of immunotherapy to treat colorectal cancer. Expert Opin Investig Drugs. 2015;24(3):329–44.CrossRefPubMedGoogle Scholar
  26. 26.
    Mocellin S, Rossi CR, Lise M, Nitti D. Colorectal cancer vaccines: principles, results, and perspectives. Gastroenterology. 2004;127(6):1821–37.CrossRefPubMedGoogle Scholar
  27. 27.
    Blankenstein T, Coulie PG, Gilboa E, Jaffee EM. The determinants of tumour immunogenicity. Nat Rev Cancer. 2012;12(4):307–13.CrossRefPubMedPubMedCentralGoogle Scholar
  28. 28.
    Keenan BP, Jaffee EM. Whole cell vaccines--past progress and future strategies. Semin Oncol. 2012;39(3):276–86.CrossRefPubMedPubMedCentralGoogle Scholar
  29. 29.
    Koido S, Ohkusa T, Homma S, Namiki Y, Takakura K, Saito K, et al. Immunotherapy for colorectal cancer. World J Gastroenterol. 2013;19(46):8531–42.CrossRefPubMedPubMedCentralGoogle Scholar
  30. 30.
    Hoover HC, Brandhorst JS, Peters LC, Surdyke MG, Takeshita Y, Madariaga J, et al. Adjuvant active specific immunotherapy for human colorectal cancer: 6.5-year median follow-up of a phase III prospectively randomized trial. J Clin Oncol. 1993;11(3):390–9.CrossRefPubMedGoogle Scholar
  31. 31.
    Harris J, Ryan L, Hoover H, Stuart R, Oken M, Benson A, et al. Adjuvant active specific immunotherapy for stage II and III colon cancer with an autologous tumor cell vaccine: Eastern Cooperative Oncology Group Study E5283. J Clin Oncol. 2000;18(1):148–57.CrossRefPubMedGoogle Scholar
  32. 32.
    Vermorken J, Claessen A, van Tinteren H, Gall H, Ezinga R, Meijer S, et al. Active specific immunotherapy for stage II and stage III human colon cancer: a randomised trial. Lancet. 1999;353(9150):345–50.CrossRefPubMedGoogle Scholar
  33. 33.
    Procaccio L, Schirripa M, Fassan M, Vecchione L, Bergamo F, Prete AA, et al. Immunotherapy in gastrointestinal cancers. Biomed Res Int. 2017;2017:4346576.CrossRefPubMedPubMedCentralGoogle Scholar
  34. 34.
    Moulton HM, Yoshihara PH, Mason DH, Iversen PL, Triozzi PL. Active specific immunotherapy with a {beta}-human chorionic gonadotropin peptide vaccine in patients with metastatic colorectal cancer: antibody response is associated with improved survival. Clin Cancer Res. 2002;8(7):2044–51.PubMedGoogle Scholar
  35. 35.
    Bilusic M, Heery CR, Arlen PM, Rauckhorst M, Apelian D, Tsang KY, et al. Phase I trial of a recombinant yeast-CEA vaccine (GI-6207) in adults with metastatic CEA-expressing carcinoma. Cancer Immunol Immunother. 2014;63(3):225–34.CrossRefPubMedGoogle Scholar
  36. 36.
    Posner MC, Niedzwiecki D, Venook AP, Hollis DR, Kindler HL, Martin EW, et al. A phase II prospective multi-institutional trial of adjuvant active specific immunotherapy following curative resection of colorectal cancer hepatic metastases: cancer and leukemia group B study 89903. Ann Surg Oncol. 2008;15(1):158–64.CrossRefPubMedGoogle Scholar
  37. 37.
    Miyagi Y, Imai N, Sasatomi T, Yamada A, Mine T, Katagiri K, et al. Induction of cellular immune responses to tumor cells and peptides in colorectal cancer patients by vaccination with SART3 peptides. Clin Cancer Res. 2001;7(12):3950–62.PubMedGoogle Scholar
  38. 38.
    Speetjens FM, Kuppen PJK, Welters MJP, Essahsah F, Voet van den Brink AMEG, Lantrua MGK, et al. Induction of p53-specific immunity by a p53 synthetic long peptide vaccine in patients treated for metastatic colorectal cancer. Clin Cancer Res. 2009;15(3):1086–95.CrossRefPubMedGoogle Scholar
  39. 39.
    Kimura T, McKolanis JR, Dzubinski LA, Islam K, Potter DM, Salazar AM, et al. MUC1 vaccine for individuals with advanced adenoma of the colon: a cancer immunoprevention feasibility study. Cancer Prev Res (Phila). 2013;6(1):18–26.CrossRefGoogle Scholar
  40. 40.
    denoue S, Hirohashi Y, Torigoe T, Sato Y, Tamura Y, Hariu H, et al. A potent immunogenic general cancer vaccine that targets survivin, an inhibitor of apoptosis proteins. Clin Cancer Res. 2005;11(4):1474–82.CrossRefGoogle Scholar
  41. 41.
    Schulze T, Kemmner W, Weitz J, Wernecke KD, Schirrmacher V, Schlag PM. Efficiency of adjuvant active specific immunization with Newcastle disease virus modified tumor cells in colorectal cancer patients following resection of liver metastases: results of a prospective randomized trial. Cancer Immunol Immunother. 2009;58(1):61–9.CrossRefPubMedGoogle Scholar
  42. 42.
    Karlsson M, Marits P, Dahl K, Dagöö T, Enerbäck S, Thörn M, et al. Pilot study of sentinel-node-based adoptive immunotherapy in advanced colorectal cancer. Ann Surg Oncol. 2010;17(7):1747–57.CrossRefPubMedPubMedCentralGoogle Scholar
  43. 43.
    Zhen Y-H, Liu X-H, Yang Y, Li B, Tang J-L, Zeng Q-X, et al. Phase I/II study of adjuvant immunotherapy with sentinel lymph node T lymphocytes in patients with colorectal cancer. Cancer Immunol Immunother. 2015;64:1083–93.CrossRefPubMedPubMedCentralGoogle Scholar
  44. 44.
    Parkhurst MR, Yang JC, Langan RC, Dudley ME, Nathan D-AN, Feldman SA, et al. T cells targeting carcinoembryonic antigen can mediate regression of metastatic colorectal cancer but induce severe transient colitis. Mol Ther. 2011;19(3):620–6.CrossRefPubMedGoogle Scholar
  45. 45.
    Correale P, Tagliaferri P, Fioravanti A, Del Vecchio MT, Remondo C, Montagnani F, et al. Immunity feedback and clinical outcome in colon cancer patients undergoing chemoimmunotherapy with gemcitabine + FOLFOX followed by subcutaneous granulocyte macrophage colony-stimulating factor and aldesleukin (GOLFIG-1 Trial). Clin Cancer Res. 2008;14(13):4192–9.CrossRefPubMedGoogle Scholar
  46. 46.
    Correale P, Botta C, Rotundo MS, Guglielmo A, Conca R, Licchetta A, et al. Gemcitabine, oxaliplatin, levofolinate, 5-fluorouracil, granulocyte-macrophage colony-stimulating factor, and interleukin-2 (GOLFIG) versus FOLFOX chemotherapy in metastatic colorectal cancer patients: the GOLFIG-2 multicentric open-label randomized phase. J Immunother. 2014;37(1):26–35.CrossRefPubMedGoogle Scholar
  47. 47.
    Greenwald RJ, Freeman GJ, Sharpe AH. The B7 family revisited. Annu Rev Immunol. 2005;23:515–48.CrossRefGoogle Scholar
  48. 48.
    Rozali EN, Hato SV, Robinson BW, Lake RA, Lesterhuis WJ. Programmed death ligand 2 in cancer-induced immune suppression. Clin Dev Immunol. 2012;2012:656340.CrossRefPubMedPubMedCentralGoogle Scholar
  49. 49.
    Topalian SL, Hodi FS, Brahmer JR, Gettinger SN, Smith DC, McDermott DF, et al. Safety, activity, and immune correlates of anti-PD-1 antibody in cancer. N Engl J Med. 2012;366(26):2443–54.CrossRefPubMedPubMedCentralGoogle Scholar
  50. 50.
    Brahmer JR, Tykodi SS, Chow LQM, Hwu W-J, Topalian SL, Hwu P, et al. Safety and activity of anti-PD-L1 antibody in patients with advanced cancer. N Engl J Med. 2012;366(26):2455–65.CrossRefPubMedPubMedCentralGoogle Scholar
  51. 51.
    Droeser RA, Hirt C, Viehl CT, Frey DM, Nebiker C, Huber X, et al. Clinical impact of programmed cell death ligand 1 expression in colorectal cancer. Eur J Cancer. 2013;49(9):2233–42.CrossRefPubMedGoogle Scholar
  52. 52.
    Heinimann K. Toward a molecular classification of colorectal cancer: the role of microsatellite instability status. Front Oncol. 2013;3:272.CrossRefPubMedPubMedCentralGoogle Scholar
  53. 53.
    Le DT, Uram JN, Wang H, Bartlett BR, Kemberling H, Eyring AD, et al. PD-1 blockade in tumors with mismatch-repair deficiency. N Engl J Med. 2015;372(26):2509–20.CrossRefPubMedPubMedCentralGoogle Scholar
  54. 54.
    Overman MJ, McDermott R, Leach JL, Lonardi S, Lenz HJ, Morse MA, et al. Nivolumab in patients with metastatic DNA mismatch repair-deficient or microsatellite instability-high colorectal cancer (CheckMate 142): an open-label, multicentre, phase 2 study. Lancet Oncol. 2017;18(9):1182–91.CrossRefPubMedPubMedCentralGoogle Scholar
  55. 55.
    Overman MJ, Lonardi S, Wong KYM, Lenz HJ, Gelsomino F, Aglietta M, et al. Durable clinical benefit with nivolumab plus ipilimumab in DNA mismatch repair-deficient/microsatellite instability-high metastatic colorectal cancer. J Clin Oncol. 2018;36(8):773–9.CrossRefGoogle Scholar
  56. 56.
    Boland PM, Hutson A, Maguire O, Minderman H, Fountzilas C, Iyer RV. A phase Ib/II study of cetuximab and pembrolizumab in RAS-wt mCRC. J Clin Oncol. 2018;36. (suppl 4S; abstr 834).CrossRefGoogle Scholar
  57. 57.
    Betts G, Jones E, Junaid S, El-Shanawany T, Scurr M, Mizen P, et al. Suppression of tumour-specific CD4+ T cells by regulatory T cells is associated with progression of human colorectal cancer. Gut. 2012;61(8):1163–71.CrossRefPubMedGoogle Scholar
  58. 58.
    Chung KY, Gore I, Fong L, Venook A, Beck SB, Dorazio P, et al. Phase II study of the anti-cytotoxic T-lymphocyte-associated antigen 4 monoclonal antibody, tremelimumab, in patients with refractory metastatic colorectal cancer. J Clin Oncol. 2010;28(21):3485–90.CrossRefPubMedGoogle Scholar
  59. 59.
    Goldberg MV, Drake CG. LAG-3 in cancer immunotherapy. Curr Top Microbiol Immunol. 2011;344:269–78.PubMedPubMedCentralGoogle Scholar
  60. 60.
    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.CrossRefPubMedGoogle Scholar
  61. 61.
    Gagliani N, Magnani CF, Huber S, Gianolini ME, Pala M, Licona-Limon P, et al. Coexpression of CD49b and LAG-3 identifies human and mouse T regulatory type 1 cells. Nat Med. 2013;19(6):739–46.CrossRefPubMedGoogle Scholar
  62. 62.
    Blackburn SD, Shin H, Haining WN, Zou T, Workman CJ, Polley A, et al. Coregulation of CD8+ T cell exhaustion by multiple inhibitory receptors during chronic viral infection. Nat Immunol. 2009;10(1):29–37.CrossRefPubMedGoogle Scholar
  63. 63.
    Chen J, Chen Z. The effect of immune microenvironment on the progression and prognosis of colorectal cancer. Med Oncol. 2014;31(8):82.CrossRefPubMedGoogle Scholar
  64. 64.
    Zhu C, Anderson AC, Schubart A, Xiong H, Imitola J, Khoury SJ, et al. The Tim-3 ligand galectin-9 negatively regulates T helper type 1 immunity. Nat Immunol. 2005;6(12):1245–52.CrossRefPubMedGoogle Scholar
  65. 65.
    Denoeud J, Moser M. Role of CD27/CD70 pathway of activation in immunity and tolerance. J Leukoc Biol. 2011;89(2):195–203.CrossRefPubMedGoogle Scholar
  66. 66.
    Jacobs J, Deschoolmeester V, Zwaenepoel K, Rolfo C, Silence K, Rottey S, et al. CD70: an emerging target in cancer immunotherapy. Pharmacol Ther. 2015;155:1–10.CrossRefPubMedGoogle Scholar
  67. 67.
    Claus C, Riether C, Schürch C, Matter MS, Hilmenyuk T, Ochsenbein AF. CD27 signaling increases the frequency of regulatory T cells and promotes tumor growth. Cancer Res. 2012;72(14):3664–76.CrossRefPubMedGoogle Scholar
  68. 68.
    Jacobs J, Zwaenepoel K, Rolfo C, Van den BJ, Deben C, Silence K, et al. Unlocking the potential of CD70 as a novel immunotherapeutic target for non-small cell lung cancer. Oncotarget. 2015;6:13462–75.CrossRefPubMedPubMedCentralGoogle Scholar
  69. 69.
    Thomas LJ, He L-Z, Marsh H, Keler T. Targeting human CD27 with an agonist antibody stimulates T-cell activation and antitumor immunity. Oncoimmunology. 2014;3(1):e27255.CrossRefPubMedPubMedCentralGoogle Scholar
  70. 70.
    Schaer DA, Hirschhorn-Cymerman D, Wolchok JD, Hodi F, O’Day S, McDermott D, et al. Targeting tumor-necrosis factor receptor pathways for tumor immunotherapy. J Immunother Cancer. 2014;2(1):7.CrossRefPubMedPubMedCentralGoogle Scholar
  71. 71.
    Pedroza-Gonzalez A, Verhoef C, Ijzermans JNM, Peppelenbosch MP, Kwekkeboom J, Verheij J, et al. Activated tumor-infiltrating CD4+ regulatory T cells restrain antitumor immunity in patients with primary or metastatic liver cancer. Hepatology. 2013;57(1):183–94.CrossRefPubMedGoogle Scholar
  72. 72.
    Schaer DA, Budhu S, Liu C, Bryson C, Malandro N, Cohen A, et al. GITR pathway activation abrogates tumor immune suppression through loss of regulatory T-cell lineage stability. Cancer Immunol Res. 2013;1(5):320–31.CrossRefPubMedGoogle Scholar
  73. 73.
    Weinberg AD, Morris NP, Kovacsovics-Bankowski M, Urba WJ, Curti BD. Science gone translational: the OX40 agonist story. Immunol Rev. 2011;244(1):218–31.CrossRefPubMedPubMedCentralGoogle Scholar
  74. 74.
    Takeda I, Ine S, Killeen N, Ndhlovu LC, Murata K, Satomi S, et al. Distinct roles for the OX40-OX40 ligand interaction in regulatory and nonregulatory T cells. J Immunol. 2004;172(6):3580–9.CrossRefPubMedGoogle Scholar
  75. 75.
    Cepowicz D, Zaręba K, Gryko M, Stasiak-Bermuta A, Kędra B. Determination of the activity of CD134 (OX-40) and CD137 (4-1BB) adhesive nolecules by means of flow cytometry in patients with colorectal cancer metastases to the liver. Polish J Surg. 2011;83(8):424–9.CrossRefGoogle Scholar
  76. 76.
    Redmond WL, Triplett T, Floyd K, Weinberg AD, Watts T, Croft M, et al. Dual anti-OX40/IL-2 therapy augments tumor immunotherapy via IL-2R-mediated regulation of OX40 expression. PLoS One. 2012;7(4):e34467.CrossRefPubMedPubMedCentralGoogle Scholar
  77. 77.
    Weinberg AD, Rivera M-M, Prell R, Morris A, Ramstad T, Vetto JT, et al. Engagement of the OX-40 receptor in vivo enhances antitumor immunity. J Immunol. 2000;164(4):2160–9.CrossRefPubMedGoogle Scholar
  78. 78.
    Gough MJ, Crittenden MR, Sarff M, Pang P, Seung SK, Vetto JT, et al. Adjuvant therapy with agonistic antibodies to CD134 (OX40) increases local control after surgical or radiation therapy of cancer in mice. J Immunother. 2010;33(8):798–809.CrossRefPubMedPubMedCentralGoogle Scholar
  79. 79.
    Pan P-Y, Zang Y, Weber K, Meseck ML, Chen S-H. OX40 ligation enhances primary and memory cytotoxic T lymphocyte responses in an immunotherapy for hepatic colon metastases. Mol Ther. 2002;6(4):528–36.CrossRefPubMedGoogle Scholar
  80. 80.
    Houot R, Levy R. T-cell modulation combined with intratumoral CpG cures lymphoma in a mouse model without the need for chemotherapy. Blood. 2009;113(15):3546–52.CrossRefPubMedPubMedCentralGoogle Scholar
  81. 81.
    Watanabe A, Hara M, Chosa E, Nakamura K, Sekiya R, Shimizu T, et al. Combination of adoptive cell transfer and antibody injection can eradicate established tumors in mice–an in vivo study using anti-OX40mAb, anti-CD25mAb and anti-CTLA4mAb-. Immunopharmacol Immunotoxicol. 2010;32(2):238–45.CrossRefGoogle Scholar
  82. 82.
    Garrison K, Hahn T, Lee W-C, Ling LE, Weinberg AD, Akporiaye ET. The small molecule TGF-β signaling inhibitor SM16 synergizes with agonistic OX40 antibody to suppress established mammary tumors and reduce spontaneous metastasis. Cancer Immunol Immunother. 2012;61(4):511–21.CrossRefPubMedGoogle Scholar
  83. 83.
    Curti BD, Kovacsovics-Bankowski M, Morris N, Walker E, Chisholm L, Floyd K, et al. OX40 is a potent immune-stimulating target in late-stage cancer patients. Cancer Res. 2013;73(24):7189–98.CrossRefPubMedPubMedCentralGoogle Scholar
  84. 84.
    Shuford WW, Klussman K, Tritchler DD, Loo DT, Chalupny J, Siadak AW, et al. 4-1BB costimulatory signals preferentially induce CD8+ T cell proliferation and lead to the amplification in vivo of cytotoxic T cell responses. J Exp Med. 1997;186(1):47–55.CrossRefPubMedPubMedCentralGoogle Scholar
  85. 85.
    Vinay DS, Kwon BS. 4-1BB signaling beyond T cells. Cell Mol Immunol. 2011;8(4):281–4.CrossRefPubMedPubMedCentralGoogle Scholar
  86. 86.
    Vinay DS, Kwon BS. Immunotherapy of cancer with 4-1BB. Mol Cancer Ther. 2012;11(5):1062–70.CrossRefPubMedGoogle Scholar
  87. 87.
    Melero I, Shuford WW, Newby SA, Aruffo A, Ledbetter JA, Hellström KE, et al. Monoclonal antibodies against the 4-1BB T-cell activation molecule eradicate established tumors. Nat Med. 1997;3(6):682–5.CrossRefPubMedGoogle Scholar
  88. 88.
    Sabel MS, Conway TF, Chen FA, Bankert RB. Monoclonal antibodies directed against the T-cell activation molecule CD137 (interleukin-A or 4-1BB) block human lymphocyte-mediated suppression of tumor xenografts in severe combined immunodeficient mice. J Immunother. 2000;23(3):362–8.CrossRefPubMedGoogle Scholar
  89. 89.
    Cepowicz D, Gryko M, Zaręba K, Stasiak-Bermuta A, Kędra B. Assessment of activity of an adhesion molecule CD134 and CD137 in colorectal cancer patients. Polish J Surg. 2011;83(12):641–5.CrossRefGoogle Scholar
  90. 90.
    Dimberg J, Hugander A, Wågsäter D. Expression of CD137 and CD137 ligand in colorectal cancer patients. Oncol Rep. 2006;15(5):1197–200.PubMedGoogle Scholar
  91. 91.
    Chen S. Rejection of disseminated metastases of colon carcinoma by synergism of IL-12 gene therapy and 4-1BB costimulation. Mol Ther. 2000;2(1):39–46.CrossRefPubMedGoogle Scholar
  92. 92.
    Segal NH, Gopal AK, Shailender B, Kohrt HE, Levy R, Pishvain MJ, et al. A phase 1 study of PF-05082566 (anti-4-1BB) in patients with advanced cancer. J Clin Oncol. 2014;32:5s.. (suppl; abstr 3007)Google Scholar
  93. 93.
    Kohrt HE, Colevas AD, Houot R, Weiskopf K, Goldstein MJ, Lund P, et al. Targeting CD137 enhances the efficacy of cetuximab. J Clin Invest. 2014;124(6):2668–82.CrossRefPubMedPubMedCentralGoogle Scholar
  94. 94.
    Houot R, Kohrt H. CD137 stimulation enhances the vaccinal effect of anti-tumor antibodies. Oncoimmunology. 2014;3(7):e941740.CrossRefPubMedPubMedCentralGoogle Scholar
  95. 95.
    Elgueta R, Benson MJ, de Vries VC, Wasiuk A, Guo Y, Noelle RJ. Molecular mechanism and function of CD40/CD40L engagement in the immune system. Immunol Rev. 2009;229(1):152–72.CrossRefGoogle Scholar
  96. 96.
    Barth RJ, Fisher DA, Wallace PK, Channon JY, Noelle RJ, Gui J, et al. A randomized trial of ex vivo CD40L activation of a dendritic cell vaccine in colorectal cancer patients: tumor-specific immune responses are associated with improved survival. Clin Cancer Res. 2010;16(22):5548–56.CrossRefPubMedPubMedCentralGoogle Scholar
  97. 97.
    Honeychurch J, Cheadle EJ, Dovedi SJ, Illidge TM. Immuno-regulatory antibodies for the treatment of cancer. Expert Opin Biol Ther. 2015;15(6):787–801.CrossRefPubMedGoogle Scholar
  98. 98.
    Georgopoulos NT, Merrick A, Scott N, Selby PJ, Melcher A, Trejdosiewicz LK. CD40-mediated death and cytokine secretion in colorectal cancer: a potential target for inflammatory tumour cell killing. Int J Cancer. 2007;121(6):1373–81.CrossRefPubMedGoogle Scholar
  99. 99.
    Palmer DH, Hussain SA, Ganesan R, Cooke PW, Wallace DMA, Young LS, et al. CD40 expression in prostate cancer: a potential diagnostic and therapeutic molecule. Oncol Rep. 2004;12(4):679–82.PubMedGoogle Scholar
  100. 100.
    Vonderheide RH, Glennie MJ. Agonistic CD40 antibodies and cancer therapy. Clin Cancer Res. 2013;19(5):1035–43.CrossRefPubMedPubMedCentralGoogle Scholar
  101. 101.
    Lal N, Beggs AD, Willcox BE, Middleton GW. An immunogenomic stratification of colorectal cancer: implications for development of targeted immunotherapy. Oncoimmunology. 2015;4(3):e976052.CrossRefPubMedPubMedCentralGoogle Scholar
  102. 102.
    Mlecnik B, Bindea G, Angell HK, et al. Integrative analyses of colorectal cancer show immunoscore is a stronger predictor of patient survival than microsatellite instability. Immunity. 2016;44(3):698–711.CrossRefPubMedGoogle Scholar
  103. 103.
    Galon J, Pages F, Marincola FM, Angell HK, Thurin M, Lugli A, et al. Cancer classification using the Immunoscore: a worldwide task force. J Transl Med. 2012;10:205.CrossRefPubMedPubMedCentralGoogle Scholar
  104. 104.
    Deschoolmeester V, Smits E, Peeters M, Vermorken JB. Status of active specific immunotherapy for stage II, stage III, and resected stage IV colon cancer. Curr Colorectal Cancer Rep. 2013;9(4):380–90.CrossRefGoogle Scholar
  105. 105.
    Ilieva KM, Correa I, Josephs DH, Karagiannis P, Egbuniwe IU, Cafferkey MJ, et al. Effects of BRAF mutations and BRAF inhibition on immune responses to melanoma. Mol Cancer Ther. 2014;13(12):2769–83.CrossRefPubMedPubMedCentralGoogle Scholar
  106. 106.
    Fields AL, Keller A, Schwartzberg L, Bernard S, Kardinal C, Cohen A, Schulz J, Eisenberg P, Forster J, Wissel P. Adjuvant therapy with the monoclonal antibody Edrecolomab plus fluorouracil-based therapy does not improve overall survival of patients with stage III colon cancer. J Clin Oncol. 2009;27(12):1941–7.CrossRefPubMedGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  • Héctor Randhall Callata-Carhuapoma
    • 1
  • Jesús García-Foncillas López
    • 1
    Email author
  1. 1.Department of OncologyUniversity Hospital Fundacion Jimenez Diaz – Autonomous University of MadridMadridSpain

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