Kanser Tedavisinde İmmunoterapi ve Radyoterapi

Yıl 2021, Cilt: 1 Sayı: 1, 16 - 27, 28.06.2021

Sema Rakici

Öz

Kanser tedavisinde immunoterapi son zamanlarda ön plana çıkmış olsa da, immün sisteminin kanser oluşumu önlenmesindeki rolü uzun zamandır bilinmektedir. İmmunoterapinin mevcut standart tedavilerle kombine edilmesi konusundaki çalışmalar yüz yıldan fazladır gündemdedir. Kanseri tedavi edenler artan hasta sayısı, uzun kontrol ve takip süreçleri ile bir
kanserle yaşayan hastalarına iyi tedavi ve iyi bir yaşam kalitesinden yararlanacak tüm şeyleri onlara sunmalıdır. Bu anlamda son araştırmalar da dikkate alındığında radyoterapi ve immünoterapi kombinasyonu (radyoimmünoterapi), birçok farklı kanser türünde tedavi yanıtını iyileştirmek için cazip bir olasılık olarak görünmektedir.
Kişinin kendi bağışıklık sisteminin gücünü, özgünlüğünü ve doğasını kullanarak, kansere karşı bağışıklık sisteminin güçlendirilebildiği bilinmektedir. Böylece immünoterapi, kanseri tedavi etmede çok güçlü araçlar sağlayabileceğinin keşfi ile zaten kanser tedavisinin kutsalları
arasında yer almaya başladı. Artık yapılması gereken, immunoterapinin mekanizmalarını anlamaya çalışarak onu radyoterapi dahil kanserin tüm klasik silahları ile kombine etme stratejileri geliştirmek olmalıdır.

Anahtar Kelimeler

İmmünoterapi, bağışıklık kontrol noktaları, immün sürveyans, kanser, radyoterapi, radyoimmünoterapi, abskopal etki, Immunotherapy, immune checkpoints, immune surveillance, cancer, radiotherapy, radioimmunotherapy, abscopal effect

Kaynakça

• 1.Dunn GP, Old LJ, Schreiber RD. The immunobiology of cancer immunosurveillance and immunoediting. Immunity. 2004;21(2):137-48.
• 2. Vivier É, Daëron M. L'immunothérapie des cancers: histoire d'une révolution médicale: Odile Jacob; 2019.
• 3. Govindan R, DeVita VT. DeVita, Hellman, and Rosenberg's Cancer: Principles & Practice of Oncology Review. Sosman JA JD, editor. Philadelphia Wolters Kluwer; 2019.
• 4. Caroll MC, Prodeus AP. Linkages of innate and adaptive immunity. Current opinion in immunology. 1998;10(1):36-40.
• 5. Carroll MC. The complement system in regulation of adaptive immunity. Nature immunology. 2004;5(10):981-6.
• 6. Anderson G, Jenkinson EJ. Lymphostromal interactions in thymic development and function. Nature Reviews Immunology. 2001;1(1):31-40.
• 7. contributors W. Cytotoxic T cell [Internet]. Wikipedia, The Free Encyclopedia. 2021 Mar 29 [cited 2021 cited 2021 Apr 12]. Available from: https://en.wikipedia.org/w/index.php?title=Cytotoxic_T_cell&oldid=1014941094.
• 8. Alexandrov LB, Nik-Zainal S, Wedge DC, Aparicio SA, Behjati S,Biankin AV, et al. Signatures of mutational processes in human cancer. Nature. 2013;500(7463):415-21.
• 9. Kelland L. The resurgence of platinum-based cancer chemotherapy. Nature Reviews Cancer. 2007;7(8):573-84.
• 10. Morgan MA, Lawrence TS. Molecular pathways: overcoming radiation resistance by targeting DNA damage response pathways. Clinical Cancer Research. 2015;21(13):2898-904.
• 11. Manic G, Obrist F, Sistigu A, Vitale I. Trial watch: targeting ATM–CHK2 and ATR–CHK1 pathways for anticancer therapy. Molecular & cellular oncology. 2015;2(4):e1012976.
• 12. Goldstein M, Kastan MB. The DNA damage response: implications for tumor responses to radiation and chemotherapy. Annual review of medicine. 2015;66:129-43.
• 13. Corrales L, McWhirter SM, Dubensky TW, Gajewski TF. The host STING pathway at the interface of cancer and immunity. The Journal of clinical investigation. 2016;126(7):2404-11.
• 14. Ashrafizadeh M, Farhood B, Musa AE, Taeb S, Najafi M. Damageassoc iated molecular patterns in tumor radiotherapy. International Immunopharmacology. 2020;86:106761.
• 15. Muroyama Y, Nirschl TR, Kochel CM, Lopez-Bujanda Z, Theodros D, Mao W, et al. Stereotactic radiotherapy increases functionally suppressive regulatory T cells in the tumor microenvironment. Cancer immunology research. 2017;5(11):992-1004.
• 16. Vanpouille-Box C, Alard A, Aryankalayil MJ, Sarfraz Y, Diamond JM, Schneider RJ, et al. DNA exonuclease Trex1 regulates radiotherapy-induced tumour immunogenicity. Nature communications. 2017;8(1):1-15.
• 17. Galluzzi L, Vitale I, Aaronson SA, Abrams JM, Adam D, Agostinis P, et al. Molecular mechanisms of cell death: recommendations of the Nomenclature Committee on Cell Death 2018. Cell Death & Differentiation. 2018;25(3):486-541.
• 18. Davidovich P, Kearney CJ, Martin SJ. Inflammatory outcomes of apoptosis, necrosis and necroptosis. Biological chemistry. 2014;395(10):1163-71.
• 19. Liao H, Wang H, Rong X, Li E, Xu R-H, Peng Y. Mesenchymal stem cells attenuate radiation-induced brain injury by inhibiting microglia pyroptosis. BioMed research international. 2017; Article ID:1948985:1-11.
• 20. Wang Z, Guo L-m, Wang S-c, Chen D, Yan J, Liu F-x, et al. Progress in studies of necroptosis and its relationship to disease processes. Pathology-Research and Practice. 2018;214(11):1749-57.
• 21. Eriksson D, Stigbrand T. Radiation-induced cell death mechanisms. Tumor Biology. 2010;31(4):363-72.
• 22. Shinomiya N. New concepts in radiation‐induced apoptosis:‘premitotic apoptosis’ and ‘postmitotic apoptosis’. Journal of cellular and molecular medicine. 2001;5(3):240-53.
• 23. Terman A, Gustafsson B, Brunk UT. Mitochondrial damage and intralysosomal degradation in cellular aging. Molecular aspects of medicine. 2006;27(5-6):471-82.
• 24. Vermes I, Haanen C, Reutelingsperger C. Flow cytometry of apoptotic cell death. Journal of immunological methods. 2000;243(1- 2):167-90.
• 25. Aksu ÖB, Şengül Ş. Immune Checkpoints and Inhibitors. Ankara Universites Tip Fakultesi Mecmuasi= Journal of Ankara University Faculty of Medicine. 2019;72(3):262-7.
• 26. Dewan MZ, Galloway AE, Kawashima N, Dewyngaert JK, Babb JS, Formenti SC, et al. Fractionated but not single-dose radiotherapy induces an immune-mediated abscopal effect when combined with anti–CTLA-4 antibody. Clinical Cancer Research. 2009;15(17):5379- 88.
• 27. Demaria S, Formenti SC. Radiation as an immunological adjuvant: current evidence on dose and fractionation. Frontiers in oncology. 2012;2:153.
• 28. Stamell EF, Wolchok JD, Gnjatic S, Lee NY, Brownell I. The abscopal effect associated with a systemic anti-melanoma immune response. International Journal of Radiation Oncology* Biology* Physics. 2013;85(2):293-5.
• 29. Dovedi SJ, Adlard AL, Lipowska-Bhalla G, McKenna C, Jones S, Cheadle EJ, et al. Acquired resistance to fractionated radiotherapy can be overcome by concurrent PD-L1 blockade. Cancer research. 2014;74(19):5458-68.26
• 30. Kwon ED, Drake CG, Scher HI, Fizazi K, Bossi A, Van den Eertwegh AJ, et al. 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. The lancet oncology. 2014;15(7):700-12.
• 31. Twyman-Saint Victor C, Rech AJ, Maity A, Rengan R, Pauken KE,Stelekati E, et al. Radiation and dual checkpoint blockade activate non-redundant immune mechanisms in cancer. Nature. 2015;520(7547):373-7.
• 32. Johnson CB, Jagsi R. The promise of the abscopal effect and the future of trials combining immunotherapy and radiation therapy. International Journal of Radiation Oncology Biology Physics. 2016;95(4):1254-6.
• 33. Alomari AK, Cohen J, Vortmeyer AO, Chiang A, Gettinger S, Goldberg S, et al. Possible interaction of anti–PD-1 therapy with the effects of radiosurgery on brain metastases. Cancer immunology research. 2016;4(6):481-7.
• 34. Sahebjam S, Johnstone PA, Forsyth PA, Arrington J, Vrionis FD, Etame AB, et al. Safety and antitumor activity of hypofractionated stereotactic irradiation (HFSRT) with pembrolizumab (Pembro) and bevacizumab (Bev) in patients (pts) with recurrent high grade gliomas: Preliminary results from phase I study. American Society of Clinical Oncology; 2016.
• 35. Segal NH, Kemeny NE, Cercek A, Reidy DL, Raasch PJ, Warren P, et al. Non-randomized phase II study to assess the efficacy of pembrolizumab (Pem) plus radiotherapy (RT) or ablation in mismatch repair proficient (pMMR) metastatic colorectal cancer (mCRC) patients. Journal of Clinical Oncology 2016 34:15_suppl, 3539-3539.
• 36. Formenti SC. The pace of progress in radiation and immunotherapy. International Journal of Radiation Oncology Biology Physics. 2016;95(4):1257-8.
• 37. Tang C, Welsh JW, De Groot P, Massarelli E, Chang JY, Hess KR, et al. Ipilimumab with stereotactic ablative radiation therapy: phase I results and immunologic correlates from peripheral T cells. Clinical Cancer Research. 2017;23(6):1388-96.
• 38. Antonia SJ, Villegas A, Daniel D, Vicente D, Murakami S, Hui R, et al. Overall survival with durvalumab after chemoradiotherapy in stage III NSCLC. New England Journal of Medicine. 2018;379(24):2342-50.
• 39. Luke JJ, Lemons JM, Karrison TG, Pitroda SP, Melotek JM, Zha Y, et al. Safety and clinical activity of pembrolizumab and multisite stereotactic body radiotherapy in patients with advanced solid tumors. Journal of Clinical Oncology. 2018;36(16):1611-18.
• 40. Theelen WS, Peulen HM, Lalezari F, van der Noort V, De Vries JF, Aerts JG, et al. Effect of pembrolizumab after stereotactic body radiotherapy vs pembrolizumab alone on tumor response in patients with advanced non–small cell lung cancer: results of the PEMBRO-RT phase 2 randomized clinical trial. JAMA oncology. 2019;5(9):1276-82.
• 41. Shaverdian N, Lisberg AE, Bornazyan K, Veruttipong D, Goldman JW, Formenti SC, et al. Previous radiotherapy and the clinical activity and toxicity of pembrolizumab in the treatment of nonsmall- cell lung cancer: a secondary analysis of the KEYNOTE-001 phase 1 trial. The Lancet Oncology. 2017;18(7):895-903.
• 42. Leach DR, Krummel MF, Allison JP. Enhancement of antitumor immunity by CTLA-4 blockade. Science. 1996;271(5256):1734-6.
• 43. Ngiow SF, McArthur GA, Smyth MJ. Radiotherapy complements immune checkpoint blockade. Cancer cell. 2015;27(4):437-8.
• 44. Shabason JE, Minn AJ, editors. Radiation and immune checkpoint blockade: from bench to clinic. Seminars in radiation oncology.2017;27(3):289-298.
• 45. Baird JR, Monjazeb AM, Shah O, McGee H, Murphy WJ, Crittenden MR, et al. Stimulating innate immunity to enhance radiation therapy–induced tumor control. International Journal of Radiation Oncology Biology Physics. 2017;99(2):362-73.
• 46. Klug F, Prakash H, Huber PE, Seibel T, Bender N, Halama N, et al. Low-dose irradiation programs macrophage differentiation to an iNOS+/M1 phenotype that orchestrates effective T cell immunotherapy. Cancer cell. 2013;24(5):589-602.
• 47. Kirsch DG, Diehn M, Kesarwala AH, Maity A, Morgan MA, Schwarz JK, et al. The future of radiobiology