免疫检查点抑制剂耐药机制及耐药后治疗策略的研究进展

doi:10.11904/j.issn.1002-3070.2017.04.012

Abstract

Abstract: Immune-checkpoint blockers(ICBs)have been well received in a variety of tumors,and the quality of patient life has improved significantly.However,the reasons why not all patients treated with ICBs benefit from lesion control,symptom improvement,and survival time.Many patients are resistant to the first time when they have been using ICBs for a period of time.This is a clinical challenge.This review lists possible causes of primary drug resistance and acquired resistance to ICBs.The primary resistance is associated with several mechanisms,including tumor microenvironment,cancer cells themselves and other related factors.The acquired resistance includes nonclassical immunoprecipitation molecules secondary overexpression,abnormalities of antigen presenting signal pathway and dysfunction of T cell activation killer.Finally,we have described a variety of possible new combination of treatment,including combined radiotherapy and chemotherapy,and combined targeted therapy with other measures.

Key words: Cancer immunotherapy, Immune-checkpoint blockers, Primary drug resistance, Acquired drug resistance

CLC Number:

R734.2

ZENG Yulan,LIU Yangyang,LIANG Jinyan,GU Feifei,LIU Li. Advances in drug resistance mechanism of immunological checkpoint inhibitors and post-drug resistant therapeutic strategy[J]. PRACTICAL ONCOLOGY JOURNAL, 2017, 31(4): 353-358.

References

1 Siegel RL,Miller KD,Jemal A.Cancer statistics,2016[J].CA Cancer J Clin,2016,66(1):7-30.
2 Joyce JA,Fearon DT.T cell exclusion,immune privilege,and the tumor microenvironment[J].Science,2015,348(6230):74-80.
3 Kelderman S,Schumacher TN,Haanen JB.Acquired and intrinsic resistance in cancer immunotherapy[J].Molecular Oncology,2014,8(6):1132-1139.
4 O′Donnell JS,Long GV,Scolyer RA,et al.Resistance to PD1/PDL1 checkpoint inhibition[J].Cancer Treatment Reviews,2017,52:71-81.
5 Robert C,Thomas L,Bondarenko I,et al.Ipilimumab plus dacarbazine for previously untreated metastatic melanoma[J].N Engl J Med,2011,364(26):2517-2526.
6 Hamid O,Robert C,Daud A,et al.Safety and tumor re-sponses with lambrolizumab(anti-PD-1)in melanoma[J].N Engl J Med,2013,369(2):134-144.
7 Hanahan D,Coussens LM.Accessories to the crime:functions of cells recruited to the tumor microenvironment[J].Cancer Cell,2012,21(3):309-322.
8 Coussens LM,Zitvogel L,Palucka AK.Neutralizing tumor-promoting chronic inflammation:a magic bullet?[J].Science,2013,339(6117):286-291.
9 Holmgaard RB,Zamarin D,Munn DH,et al.Indoleamine 2,3-dioxygenase is a critical resistance mechanismin anti-tumor T cell immunotherapy targeting CTLA-4[J].J Exp Med,2013,210(7):1389-1402.
10 Nagarsheth N,Peng D,Kryczek I,et al.PRC2 epigenetically silences Th1-Type chemokines to suppress effector T-cell trafficking in colon cancer[J].Cancer Res,2016,76(2):275-282.
11 Diamond MS,Kinder M,Matsushita H,et al.Type I interferon is selectively required by dendritic cells for immune rejection of tumors[J].J Exp Med,2011,208(10):1989-2003.
12 Fuertes MB,Kacha AK,Kline J,et al.Host type I IFN signals are required for antitumor CD8+ T cell responses through CD8α+ dendritic cells[J].J Exp Med,2011,208(10),2005-2016.
13 Spranger S,Bao R,Gajewski TF.Melanoma-intrinsic beta-catenin signalling prevents anti-tumour immunity[J].Nature,2015,523(7559):231-235.
14 Ansell SM,Lesokhin AM,Borrello I,et al.PD-1 blockade with nivolumab in relapsed or refractory Hodgkin′s lymphoma[J].N Engl J Med,2015,372(4):311-319.
15 Chen N,Fang W,Zhan J,et al.Up-regulation of PD-L1 by egfr activation mediates the immune escape in GFR-driven NSCLC:Implication for optional immune targeted therapy for NSCLC patients with EGFR mutation[J].J Thorac Oncol,2015,10(6):910-923.
16 Zelenay S,van der Veen AG,Bottcher JP,et al.Cyclooxygenase-dependent tumor growth through evasion of immunity[J].Cell,2015,162(6):1257-1270.
17 Chang CH,Qiu J,O′Sullivan D,et al.Metabolic competition in the tumor microenvironment is a driver of cancer progression[J].Cell,2015,162(6):1229-1241.
18 Yang W,Bai Y,Xiong Y,et al.Potentiating the antitumour response of CD8+ T cells by modulating cholesterol metabolism[J].Nature,2016,531(7596),651-655.
19 Rizvi NA,Hellmann MD,Snyder A,et al.Cancer immunology.Mutational landscape determines sensitivity to PD-1 blockade in non-small cell lung cancer[J].Science,2015,348(6230):124-128.
20 Le DT,Uram JN,Wang H,et al.PD-1 blockade in tumors with mismatch-repair deficiency[J].N Engl J Med,2015,372(26):2509-2520.
21 Rizvi NA,Hellmann MD,Snyder A,et al.Mutational landscape determines sensitivity to PD-1 blockade in non-small cell lung cancer[J].Science,2015,348(6230):124-128.
22 Melero I,Lasarte JJ.Genetic basis for clinical response to CTLA-4 blockade[J].N Engl J Med,2015,372(8):783.
23 Yadav M,Jhunjhunwala S,Phung QT,et al.Predicting immunogenic tumour mutations by combining mass spectrometry and exome sequencing[J].Nature,2014,515(7528):572-576.
24 Gubin MM,Zhang X,Schuster H,et al.Checkpoint blockade cancer immunotherapy targets tumour-specific mutant antigens[J].Nature,2014,515(7528):577-581.
25 Brahmer J,Reckamp KL,Baas P,et al.Nivolumab versus Docetaxel in advancedsquamous-cell non-small-cell lung cancer[J].N Engl J Med,2015,373(2):123-135.
26 Brahmer J,Reckamp KL,Baas P,et al.Nivolumab versus docetaxel in advanced squamous-cell non-small-cell lung cancer[J].N Engl J Med,2015,373(3):123-135.
27 Ilie M,Long-Mira E,Bence C,et al.Comparative study of the PD-L1 status between surgically resected specimens and matched biopsies of NSCLC patients reveal major discordances:a potential issue for anti-PD-L1 therapeutic strategies[J].Ann Oncol,2016,27(1):147-153.
28 Kataoka K,Shiraishi Y,Takeda Y,et al.Aberrant PD-L1 expression through 3′-UTR disruption in multiple cancers[J].Nature,2016,534(7607):402-406.
29 Gao J,Shi LZ,Zhao H,et al.Loss of IFN-gamma pathway genes in tumor cells as a mechanism of resistance to anti-CTLA-4 therapy[J].Cell,2016,167(2):397-404.
30 Pitt JM,Vetizou M,Daillere R,et al.Resistance mechanisms to immune-checkpoint blockade in cancer:tumor-intrinsic and-extrinsic factors[J].Immunity,2016,44(6):1255-1269.
31 Zaretsky JM,Garcia-Diaz A,Shin DS,et al.Mutations associated with acquired resistance to PD-1 blockade in melanoma[J].N Engl J Med,2016,375(9):819-829.
32 Koyama S,Akbay EA,Li YY,et al.Adaptive resistance to therapeutic PD-1 blockade is associated with upregulation of alternative immune checkpoints[J].Nature Communications,2016,7:10501.
33 Miao D,Adeegbe D,Rodig SJ,et al.Response and oligoclonal resistance to pembrolizumab in uterine leiomyosarcoma:Genomic,neoantigen,and immunohistochemical evaluation[J].Chicago:ASCO Annual Meeting,2016.
34 Vatner RE,Cooper BT,Vanpouille-Box C,et al.Combinations of immunotherapy and radiation in cancer therapy[J].Front Oncol,2014,4:325.
35 Twyman-Saint Victor C,Rech AJ,Maity A,et al.Radiation and dual checkpoint blockade activate non-redundant immune mechanisms in cancer[J].Nature,2015,520(7547):373-377.
36 Bernstein MB,Krishnan S,Hodge JW,et al.Immunotherapy and stereotactic ablative radiotherapy(ISABR):a curative approach?[J].Nature Reviews Clinical Oncology,2016,13(8):516-524.
37 Twyman-Saint Victor C,Rech AJ,Maity A,et al.Radiation and dual checkpoint blockade activate non-redundant immune mechanisms in cancer[J].Nature,2015,520(7547):373-377.
38 Antonia SJ,Brahmer JR,Gettinger SN,et al.Nivolumab(anti-PD-1;BMS-936558,ONO-4538)in combination with platinum-based doublet chemotherapy(PT-DC)in advanced non-small cell lung cancer(NSCLC)[J].Chicago:ASCO Annual Meeting,2015.
39 Vincent J,Mignot G,Chalmin F,et al.5-Fluorouracil selectively kills tumor-associated myeloid-derived suppressor cells resulting in enhanced T cell-dependent antitumor immunity[J].Cancer Res,2010,70:3052-3061.
40 Tesniere A,Schlemmer F,Boige V,et al.Immunogenic death of colon cancer cells treated with oxaliplatin[J].Oncogene,2010,29(4):482-491.
41 Hughes PE,Caenepeel S,Wu LC.Targeted therapy and checkpoint immunotherapy combinations for the treatment of cancer[J].Trends Immunol,2016,37(7):462-476.
42 Sharma P,Allison JP.Immune checkpoint targeting in cancer therapy:toward combination strategies with curative potential[J].Cell,2015,161(2):205-2144.
43 Wahid M,Akhter N,Jawed A,et al.Pembrolizumab′s non-cross resistance mechanism of action successfully overthrown ipilimumab[J].Crit Rev Oncol Hematol,2017,111:1-6.
44 Spagnolo F,Ghiorzo P,Orgiano L,et al.BRAF-mutant melanoma:treatment approaches,resistance mechanisms,and diagnostic strategies[J].Onco Targets Ther,2015,8:157-168.
45 Oxnard GR,Ramalingam SS,Ahn M,et al.Preliminary results of TATTON,a multi-arm phase Ib trial of AZD9291 combined with MEDI4736,AZD6094 or selumetinib in EGFR-mutant lung cancer[J].Chicago:ASCO Annual Meeting,2015.
46 Wolchok JD,Kluger H,Callahan MK,et al.Nivolumab plus ipilimumab in advanced melanoma[J].N Engl J Med,2013,369(2):122-133.
47 Topalian SL,Taube JM,Anders RA,et al.Mechanism-driven biomarkers to guide immune checkpoint blockade in cancer therapy[J].Nat Rev Cancer,2016,16(5):275-287.
48 Puzanov I,Milhem MM,Minor D,et al.Talimogene laherparepvec in combination with ipilimumab in previously untreated,unresectable stage ⅢB-Ⅳ melanoma[J].J Clin Oncol,2016,34(22):2619-2626.
49 Chapuis AG,Roberts IM,Thompson JA,et al.T-cell therapy using interleukin-21-primed cytotoxic T-cell lymphocytes combined with cytotoxic T-cell lymphocyte antigen-4 blockade results in long-term cell persistence and durable tumor regression[J].J Clin Oncol,2016[Epub ahead of print].

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Advances in drug resistance mechanism of immunological checkpoint inhibitors and post-drug resistant therapeutic strategy

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