Colorectal Cancer And Immunotherapy

Öz

Colorectal cancer (CRC) is the third most common cancer in both genders and the third most common cause of cancer related deaths. One million CRC patients are newly diagnosed annually and more than 20% of them are metastatic at the time of diagnosis. About 50% of patients diagnosed at an early stage develop relapse and metastasis on follow up. Although new advances in the treatment increased the survival rates of patients with metastatic disease, need for new treatment choices is still present. Increased knowledge on the preventive role of immune system in tumor formation, growth and metastasis draws attention to this field for new therapies. Since treatment modalities under the heading of immunotherapy yield favorable responses in many types of cancer, its use in CRC is also investigated. The aim of this study is to analyze known immune response mechanisms against CRC and immune escape mechanisms developed by tumor and present knowledge on current and future immunotherapy modalities for CRC.

Anahtar Kelimeler

• Colon,Rectum,Cancer,Immunity

Kolorektal Kanser ve İmmünoterapi

Öz

Kolorektal kanser (KRK), her iki cinste üçüncü en sık görülen kanser türü olup, kanser ilişkili ölüm nedenleri arasında da yine üçüncü sırada yer almaktadır. Her yıl yeni tanı alan yaklaşık 1 milyon KRK hastasının % 20’sinden fazlası tanı anında metastatik iken, erken evrede tanı alan hastaların yaklaşık % 50’sinde takipte relaps ve metastaz geliştiği izlenmektedir. Son yıllarda tedavi alanındaki gelişmeler metastatik safhadaki hastaların sağ kalım oranlarını arttırmış olsa da, yeni tedavi seçeneklerine olan ihtiyaç devam etmektedir. İmmün sistemin tümörün oluşumu, büyümesi ve metastazının önlenmesinde önemli rol oynayabileceğine dair artan bilgiler dikkatleri tedavi açısından bu alana çekmektedir. İmmünoterapi başlığı altındaki tedaviler, pek çok kanser türünde olumlu yanıtlar alınması nedeniyle KRK’de de araştırılmaktadır. Bu yazının amacı; KRK’e karşı bilinen immün yanıt mekanizmaları ve tümör tarafından geliştirilen immün kaçış mekanizmalarının analizi ve KRK için günümüz ve gelecekteki immünoterapi seçenekleri hakkında bilgileri sunabilmektir.

Anahtar Kelimeler

• Kolon,Rektum,Cancer,İmmünite

Kaynakça

1. Referans1 Dunn GP, Bruce AT, Ikeda H, et al. Cancer immunoediting: from immunosurveillance to tumor escape. Nat Immunol 2002;3:991-998.
2. Referans2 Pernot S, Terme M, Voron T, et al. Colorectal cancer and immunity: what we know and perspectives. World J Gastroenterol 2014;20:3738-3750.
3. Referans3 Ohtani H. Focus on TILs: prognostic significance of tumor infiltrating lymphocytes in human colorectal cancer. Cancer Immun 2007;7:4.
4. Referans4 Weng D, Song B, Durfee J et al. Induction of cytotoxic T lymphocytes against ovarian cancer-initiating cells. Int J Cancer 2011;129:1990-2001.
5. Referans5 Takahara A, Koido S, Ito M et al. Gemcitabine enhances Wilms’ tumor gene WT1 expression and sensitizes human pancreatic cancer cells with WT1-specific T-cell-mediated antitumor immune response. Cancer Immunol Immunother 2011;60:1289-1297.
6. Referans6 Weng D, Song B, Koido S, Calderwood SK, Gong J. Immunotherapy of radioresistant mammary tumors with early metastasis using molecular chaperone vaccines combined with ionizing radiation. J Immunol 2013;191:755-763.
7. Referans7 Grande C, Firvida JL, Navas V, Casal J. Interleukin-2 for the treatment of solid tumors other than melanoma and renal cell carcinoma. Anticancer Drugs 2006;17:1–12.
8. Referans8 Noguchi T, Ritter G, Nishikawa H. Antibody-based therapy in colorectal cancer. Immunotherapy 2013;5:533-545.

9. Referans9 Pardoll DM. The blockade of immune checkpoints in cancer immunotherapy. Nat Rev Cancer 2012;12:252-264.
10. Referans10 Ellebaek E, Andersen MH, Svane IM, Straten PT. Immunotherapy for metastatic colorectal cancer: Present status and new options Scand Gastroenterol 2012;47:315–332.
11. Referans11 Corvaisier M, Moreau-Aubry A, Diez E et al. V gamma 9V delta 2 T cell response to colon carcinoma cells. J Immunol 2005;175:5481-5488.
12. Referans12 Kabelitz D, Wesch D, Pitters E, Zöller M. Potential of human gammadelta T lymphocytes for immunotherapy of cancer. Int J Cancer 2004;112:727-732.
13. Referans13 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;8:2044-2051.
14. Referans14 Posner MC, Niedzwiecki D, Venook AP 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;15:158-164.
15. Referans15 Toubaji A, Achtar M, Provenzano M et al. Pilot study of mutant ras peptide-based vaccine as an adjuvant treatment in pancreatic and colorectal cancers. Cancer Immunol Immunother 2008;57:1413-1420.
16. Referans16 Kimura T, McKolanis JR, Dzubinski LA et al. MUC1 vaccine for individuals with advanced adenoma of the colon: a cancer immunoprevention feasibility study. Cancer Prev Res (Phila) 2013;6:18-26.
17. Referans17 Speetjens FM, Kuppen PJ, Welters MJ 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;15:1086-1095.
18. Referans18 Koido, Ohkuso T, Homma S et al. Immunotherapy for colorectal cancer World J Gastroenterol 2013:14;19:8531-8542.
19. Referans19 Schlag P, Manasterski M, Gerneth T et al. Active specific immunotherapy with Newcastle-disease-virus-modified autologous tumor cells following resection of liver metastases in colorectal cancer. First evaluation of clinical response of a phase II-trial. Cancer Immunol Immunother 1992;35:325–330.
20. Referans20 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;58:61–69.
21. Referans21 Hoover HC Jr, Brandhorst JS, Peters LC 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;11:390–399.
22. Referans22 Vermorken JB, Claessen AM, Van TH et al. Active specific immunotherapy for stage II and stage III human colon cancer: a randomised trial. Lancet 1999;353:345–350.
23. Referans23 Hanna MG Jr, Hoover HC Jr, Vermorken JB, Harris JE, Pinedo HM. Adjuvant active specific immunotherapy of stage II and stage III colon cancer with an autologous tumor cell vaccine: first randomized phase III trials show promise. Vaccine 2001;19(17–19):2576–2582.
24. Referans24 Palucka K, Banchereau J. Cancer immunotherapy via dendritic cells. Nat Rev Cancer 2012;12:265-277
25. Referans25 Liu Y, Zhang W, Zhang B, Yin X, Pang Y. DC vaccine therapy combined concurrently with oral capecitabine in metastatic colorectal cancer patients. Hepatogastroenterology 2013;60:23-27.
26. Referans26 Morse MA, Niedzwiecki D, Marshall JL et al. A randomized phase II study of immunization with dendritic cells modified with poxvectors encoding CEA and MUC1 compared with the same poxvectors plus GM-CSF for resected metastatic colorectal cancer. Ann Surg 2013;258:879-886.
27. Referans27 Barth RJ, Fisher DA, Wallace PK 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;16:5548-5556.
28. Referans28 Fong L, Hou Y, Rivas A et al. Altered peptide ligand vaccination with Flt3 ligand expanded dendritic cells for tumor immunotherapy. Proc Natl Acad Sci USA 2001;98:8809-8814.
29. Referans29 Munn DH, Mellor AL. Indoleamine 2,3-dioxygenase and tumor-induced tolerance. J Clin Invest. 2007;117:1147–1154.
30. Referans30 Sorensen RB, Hadrup SR, Svane IM, Hjortso MC, Thor SP, Andersen MH. Indoleamine 2,3-dioxygenase specific, cytotoxic T cells as immune regulators. Blood 2011;117:2200–2210.
31. Referans31 Marshall JL, Gulley JL, Arlen PM, Beetham PK, et al. Phase I study of sequential vaccinations with fowlpox-CEA(6D)-TRICOM alone and sequentially with vaccinia-CEA(6D)-TRICOM, with and without granulocyte-macrophage colony-stimulatingfactor, in patients with carcinoembryonic antigenexpressing carcinomas. J Clin Oncol 2005;23:720-731. Referans32 Kaufman HL, Lenz HJ, Marshall J, et al. Combination chemotherapy and ALVAC-CEA/B7.1 vaccine in patients with metastatic colorectal cancer. Clin Cancer Res 2008;14:4843-4849.
32. Referans33 Restifo NP, Dudley ME, Rosenberg SA. Adoptive immunotherapy for cancer: harnessing the T cell response. Nat Rev Immunol 2012;12:269–281.
33. Referans34 Karlsson M, Marits P, Dahl K et al. Pilot study of sentinel-node-based adoptive immunotherapy in advanced colorectal cancer. Ann Surg Oncol 2010;17:1747-1757.
34. Referans35 Parkhurst MR, Yang JC, Langan RC et al. T cells targeting carcinoembryonic antigen can mediate regression of metastatic colorectal cancer but induce severe transient colitis. Mol Ther 2011;19:620-62.
35. Referans36 Morgan RA, Yang JC, Kitano M, Dudley ME, Laurencot CM, Rosenberg SA. Case report of a serious adverse event following the administration of T cells transduced with a chimeric antigen receptor recognizing ERBB2. Mol Ther 2010;18:843-851.