恶性肿瘤免疫检查点抑制剂耐药机制的研究进展
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摘要
肿瘤免疫治疗是利用机体免疫系统特异性识别和杀伤的原理来达到治疗肿瘤的目的。在各种免疫治疗的方式中,免疫检查点抑制剂(Immune-checkpoint inhibitors,ICIs)在多种肿瘤的治疗中获得了较好的疗效。然而,与靶向治疗一样,免疫治疗在带给我们希望的同时,也不可避免的出现了耐药的难题。从发生时间来看,肿瘤免疫治疗耐药可分为原发性耐药、适应性耐药和获得性耐药,本文将就恶性肿瘤免疫检查点抑制剂的耐药机制进行综述。
Tumor immunotherapy is the use of the body's immune system to recognize and eliminate cancer cells. In various immunotherapy approaches,immune checkpoint inhibitors(ICIs) have achieved better efficacy in the treatment of various tumors. However,like targeted therapies,immunotherapy has given us hope while at the same time it has inevitably emerged as a drug resistance problem. Judging from the time of occurrence,resistance to tumor immunotherapy can be divided into primary,adaptive,and acquired. This article will review the mechanism of drug resistance of malignant tumor immune checkpoint inhibitors.
Tumor immunotherapy is the use of the body's immune system to recognize and eliminate cancer cells. In various immunotherapy approaches,immune checkpoint inhibitors(ICIs) have achieved better efficacy in the treatment of various tumors. However,like targeted therapies,immunotherapy has given us hope while at the same time it has inevitably emerged as a drug resistance problem. Judging from the time of occurrence,resistance to tumor immunotherapy can be divided into primary,adaptive,and acquired. This article will review the mechanism of drug resistance of malignant tumor immune checkpoint inhibitors.
引文
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[2]艾斌.免疫检查点抑制剂在肿瘤治疗中的应用[J].医学与哲学,2015,36(2B):519.
[3]Joyce JA,Fearon DT.T cell exclusion,immune privilege,and the tumor microenvironment[J].Science,2015,348(6230):74-80.
[4]S.L.Topalian.F.S.Hodi.J.R.Brahmer,S.N.Gettinger,D.C.Smith,D.F.Mc Dermott,et al.,Safety,activity,and immune correlates of anti-PD-1antibody in cancer,N[J].Engl.j.Med,2012,366(26):2443-2454.
[5]W.Zou,J.D.Wolchok,L.Chen,PD-L1(B7-H1)and PD-1 pathway blockade for cancer therapy:Mechanisms,response biomarkers,and combinations,Sci.Transl[J].Med,2016,8(328):324.
[6]许斌,胡梦雪,宋启斌恶性肿瘤免疫检查点抑制剂耐药机制及临床应用[J].China Cancer,2017,26(9).
[7]张婷婷,李林玉,宋拯,等.肿瘤免疫治疗的耐药机制研究进展[J].中华微生物学和免疫学杂志,2017,37(11).
[8]Jianjun Gao,Lewis Zhichang et al.Woodman,Pei-Ling Chen,Patrick Hwu,James P.Allison,Andrew Futreal,Jennifer A.Wargo,Padmanee Sharma.Loss of IFN-γPathway Genes in Tumor Cells as a Mechanism of Resistance to Anti-CTLA-4 Therapy[J].Cell,2016,167(2).
[9]Shin DS,Ribas A.The evolution of checkpoint blockade as a cancer therapy:what’s here,what’s next?[J].Curr Opin Immunol,2015,33:23-35.
[10]Qiaohong Wang,Xia Wu.Primary and acquired resistance to PD-1/PDL1 blockade in cancer treatment[J].International Immunopharmacology,2012,46:210-219.
[11]Sakaguchis,Yamaguchi T,Nomura T,et al.Regulatory T cells and immune to lerance[J].Cell,2008,133(5):775787.
[12]Linehan DC,Goedegebuure PS.CD25+CD4+regulatory Tcells in cancer[J].Immunol Res,2005,32:155-168.
[13]O'Donnell JS,Long GV,Scolyer RA,et al.Resistance to PD1/PDL1checkpointinhibition[J].Cancer Treat Rev,2017,52:71-81.
[14]Guoliang Yang,Wenyan Shen,Yan zhang,et al.Accumulation of myeloid-derived suppressor cells(MDSCs)induced by low levels of IL-6correlates with poor prognosis in bladder cancer[J].Oncotarget,Advance Publications,2017.
[15]何林燕.肿瘤相关巨噬细胞及其在肿瘤中的作用[J].现代免疫学,2014,34(1).
[16]Fritz JM,Tennis MA,Orlicky DJ,et al.Depletion of tumorassociated macrophages slows the growth of chemically induced mouse lung adenocarcinomas[J].Front Immunol,2014,5:587.
[17]Zaretsky JM,Garcia-Diaz A,Shin DS,et al.Mutations associated with acquired resistance to PD-1 blockade in melanoma[J].NEngl JMed,2016,375(9):819-829.
[18]董忠谊,钟文昭.抗PD-1免疫治疗获得性耐药机制-新的免疫检查点Tl M3激活[J].询证医学,2016,16(3).
[19]Scott Gettinger,Jungmin Choi,Katherine Hastings,et al.Impaired HLA Class I Antigen Processing and Presentation as a Mechanism of Acquired Resistance to Immune Checkpoint Inhibitors in Lung Cancer[A].Research.On October 12,2017.?2017 American Association for Cancercancerdiscovery.aacrjournals.org