放疗协同免疫检查点阻滞剂治疗肿瘤的机制

国际肿瘤学杂志››2017,Vol. 44››Issue (3): 209-212.doi:10.3760/cma.j.issn.1673422X.2017.03.013

放疗协同免疫检查点阻滞剂治疗肿瘤的机制

陈泽宏,苏如雄,杨子科,康世均

510515 广州，南方医科大学中西医结合医院肿瘤科（陈泽宏、杨子科）；南方医科大学附属普宁市人民医院药剂科（苏如雄）；南方医科大学南方医院肿瘤科（康世均）

出版日期:2017-03-08发布日期:2017-02-28
通讯作者:康世均 E-mail:junekfm@yahoo.com
基金资助:

国家自然科学基金（81372449）

Mechanisms of cancer treatment by radiotherapy combined with immune checkpoint blockade

Chen Zehong, Su Ruxiong, Yang Zike, Kang Shijun

Department of Oncology, Traditional Chinese MedicineIntegrated Hospital, Southern Medical University, Guangzhou 510515, China

Online:2017-03-08Published:2017-02-28
Contact:Kang Shijun E-mail:junekfm@yahoo.com
Supported by:

National Natural Science Foundation of China

(81372449)

摘要/Abstract

摘要：随着对肿瘤免疫机制的深入研究，学者们注意到了放疗激活机体产生全身免疫效应的现象，改变了放疗是“免疫抑制性”的片面认识。然而，放疗虽能增强机体的抗肿瘤免疫，在临床上，接受放疗的患者仍避免不了复发、转移。研究表明，这与肿瘤微环境诱导的免疫检查点通路异常激活密切相关。因此，将放疗与免疫检查点阻滞剂联合应用，改善肿瘤微环境，能提高肿瘤治疗效果。

关键词:放射疗法,肿瘤逃逸,免疫检查点阻滞剂

Abstract:With the further researches on the immune mechanisms in tumor, more and more scholars notice the phenomenon that radiation activates the immunity, and find that "radiotherapy causes immunity suppression" is onesided. Although body′s antitumor immunity can be enhanced by radiotherapy, in clinical, we observe that patients who receive radiotherapy cannot avoid tumor recurrence and metastasis. Researches show that tumor microenvironment makes the immune checkpoint pathway abnormally activated. Therefore, the combination of radiotherapy and immune checkpoint inhibitor can change the tumor microenvironment, and can improve the therapeutic effect.

Key words:Radiotherapy,Tumor escape,Immune checkpoint blockade

陈泽宏,苏如雄,杨子科,康世均. 放疗协同免疫检查点阻滞剂治疗肿瘤的机制[J]. 国际肿瘤学杂志, 2017, 44(3): 209-212.

Chen Zehong, Su Ruxiong, Yang Zike, Kang Shijun. Mechanisms of cancer treatment by radiotherapy combined with immune checkpoint blockade[J]. Journal of International Oncology, 2017, 44(3): 209-212.

参考文献

［1］ HerterSprie GS, Koyama S, Korideck H, et al. Synergy of radiotherapy and PD1 blockade in Krasmutant lung cancer［J］. JCI Insight, 2016, 1(9): e87415. ［2］ McNutt M. Cancer immunotherapy［J］. Science, 2013, 342(6165): 1417. DOI: 10.1126/science.1249481. ［3］ Shiao SL, Ruffell B, Denardo DG, et al. TH2polarized CD4(+) T cells and macrophages limit efficacy of radiotherapy［J］. Cancer Immunol Res, 2015, 3(5): 518-525. DOI: 10.1158/23266066.CIR140232. ［4］ Levy A, Chargari C, Marabelle AA, et al. Can immunostimulatory agents enhance the abscopal effect of radiotherapy?［J］. Eur J Cancer, 2016, 62: 36-45. DOI: 10.1016/j.ejca.2016.03.067. ［5］ Reynders K, Illidge T, Siva S, et al. The abscopal effect of local radiotherapy: using immunotherapy to make a rare event clinically relevant［J］. Cancer Treat Rev, 2015, 41(6): 503-510. DOI: 10.1016/j.ctrv.2015.03.011. ［6］ Formenti SC, Demaria S. Systemic effects of local radiotherapy［J］. Lancet Oncol, 2009, 10(7): 718-726. DOI: 10.1016/S14702045(09)700828. ［7］ Bos PD, Plitas G, Rudra D, et al. Transient regulatory T cell ablation deters oncogenedriven breast cancer and enhances radiotherapy［J ］. J Exp Med, 2013, 210(11): 2435-2466. DOI: 10.1084/jem.20130762. ［8］ Zeng J, See AP, Phallen J, et al. AntiPD1 blockade and stereotactic radiation produce longterm survival in mice with intracranial gliomas［J］. Int J Radiat Oncol Biol Phys, 2013, 86(2): 343- 349. DOI: 10.1016/j.ijrobp.2012.12.025. ［9］ Scheithauer H, Belka C, Lauber K, et al. Immunological aspects of radiotherapy［J］. Radiat Oncol, 2014, 9: 185. DOI: 10.1186/1748717X9 185. ［10］ Weiss EM, Wunderlich R, Ebel N, et al. Selected antitumor vaccines merit a place in multimodal tumor therapies［J］. Front Oncol, 2012, 2: 132. DOI: 10.3389/fonc.2012.00132. ［11］ Green DR, Ferguson T, Zitvogel LA. Immunogenic and tolerogenic cell death［J］. Nat Rev Immunol, 2009, 9(5): 353363. DOI: 10.1038/nri2545. ［12］ Zitvogel L, Kepp O, Kroemer G. Decoding cell death signals in inflammation and immunity［J］. Cell, 2010, 140(6): 798-804. DOI: 10.1016/j.cell.2010.02.015. ［13］ Tang C, Wang XH, Soh H, et al. Combining radiation and immunotherapy: a new systemic therapy for solid tumors?［J］. Cancer Immunol Res, 2014, 2(9): 831-838. DOI: 10.1158/23266066.CIR140069. ［14］ Matsumura S, Wang B, Kawashima N, et al. Radiationinduced CXCL16 release by breast cancer cells attracts effector T cells［J］. J Immunol, 2008, 181(5): 3099-3107. ［15］ Pilones KA, VanpouilleBox C, Demaria S. Combination of radiotherapy and immune checkpoint inhibitors［J］. Semin Radiat Oncol, 2015, 25(1): 28-33. DOI: 10.1016/j.semradonc.2014.07.004. ［16］ Marincola FM, Jaffee EM, Hicklin DJ, et al. Escape of human solid tumors from Tcell recognition: molecular mechanisms and functional significance［J］. Adv Immunol, 2000, 74: 181-273. ［17］ Apetoh L, Ghiringhelli F, Tesniere AA, et al. Tolllike receptor 4 dependent contribution of the immune system to anticancer chemotherapy and radiotherapy［J］. Nat Med, 2007, 13(9): 1050-1059. DOI: 10.1038/nm1622. ［18］ Reits EA, Hodge JW, Herberts CA, et al. Radiation modulates the peptide repertoire, enhances MHC class Ⅰ expression, and induces successful antitumor immunotherapy［J］. J Exp Med, 2006, 203(5): 1259-1271. DOI: 10.1084/jem.20052494. ［19］ Formenti SC, Demaria S. Combining radiotherapy and cancer immunotherapy: a paradigm shift［J］. J Natl Cancer Inst, 2013, 105(4): 256 -265. DOI: 10.1093/jnci/djs629. ［20］ Bumette B, Weichselbaum RR. The immunology of ablative radiation［J ］. Semin Radiat Oncol, 2015, 25(1): 40-45. DOI: 10.1016/j.semradonc.2014.07.009. ［21］ RodriguezRuiz ME, Rodriguez I, Garasa SA, et al. Abscopal effects of radiotherapy are enhanced by combined immunostimulatory mAbs and are dependent on CD8 T cells and crosspriming［J］. Cancer Res, 2016, 76(20): 5994-6005. DOI: 10.1158/00085472.CAN160549. ［22］ Mole RH. Whole body irradiation; radiobiology or medicine?［J］. Br J Radiol, 1953, 26(305): 234-241. ［23］ Kalbasi A, June CH, Haas N, et al. Radiation and immunotherapy: a synergistic combination［J］. J Clin Invest, 2013, 123(7): 2756-2763. DOI: 10.1172/JCI69219. ［24］ Gabrilovich DI, OstrandRosenberg S, Bronte V. Coordinated regulation of myeloid cells by tumours［J］. Nat Rev Immunol, 2012, 12(4): 253-268. DOI: 10.1038/nri3175. ［25］ Deng L, Liang H, Burnette B, et al. Irradiation and antiPDL1 treatment synergistically promote antitumor immunity in mice［J］. J Clin Invest, 2014, 124(2): 687-695. DOI: 10.1172/JCI67313. ［26］ Park SS, Dong HD, Liu X, et al. PD1 restrains radiotherapyinduced abscopal effect［J］. Cancer Immunol Res, 2015, 3(6): 610-619. DOI: 10.1158/23266066.CIR140138. ［27］ Demaria S, Kawashima N, Yang AM, et al. Immunemediated inhibition of metastases after treatment with local radiation and CTLA4 blockade in a mouse model of breast cancer［J］. Clin Cancer Res, 2005, 11(2 Pt 1): 728 -734.

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