肺癌T细胞过继免疫治疗和新抗原研究进展

摘要
图/表
参考文献(0)
相关文章 (15)

全文: PDF (716 KB) HTML (1 KB)
输出: BibTeX | EndNote (RIS)

摘要［摘要］T细胞杀伤肿瘤细胞是肿瘤免疫治疗的关键事件。最近抗程序性死亡受体1(programmed death receptor1，PD1)/PD1配体1(PD1 ligand，PDL1)抗体等免疫检查点抑制剂在肺癌临床治疗中取得成功，显示其在癌症免疫疗法中起关键作用。但是，并非所有患者都能从免疫疗法中获得有效的反应。液体活检潜在的生物标志物可能有助于鉴定从免疫治疗中受益最大的患者。具有高肿瘤突变负荷的肿瘤已确认为免疫检查点抑制剂治疗的适应证。肿瘤突变负荷水平与新抗原数量呈正相关，新抗原成为肺癌免疫治疗成功的关键。自体基因编码免疫原性肿瘤新抗原已成为一种免疫过继治疗的重要靶标，而针对新抗原的T细胞受体工程改造是用于治疗肺癌的过继细胞疗法的新选择。

	服务

	把本文推荐给朋友
	加入我的书架
	加入引用管理器
	E-mail Alert
	RSS
	作者相关文章
	蔡良良1
	2
	钱莉1
	2

关键词 ： T细胞, 肿瘤新抗原, 肺癌, 肿瘤免疫治疗, 肿瘤免疫微环境, T细胞受体改造

收稿日期: 2020-06-28

基金资助:国家自然科学基金资助项目(81771689)

通讯作者: 钱莉(通讯作者)，教授，博士生导师，E-mail：qianl@yzu.edu.cn

作者简介: 蔡良良(1988—)，男，博士，讲师，主要从事肺癌微环境研究；

引用本文:

蔡良良1,2，钱莉1,2. 肺癌T细胞过继免疫治疗和新抗原研究进展[J]. 江苏大学学报:医学版, 2020, 30(05): 386-389.

链接本文:

http://zzs.ujs.edu.cn/xbyxb/CN/ 或 http://zzs.ujs.edu.cn/xbyxb/CN/Y2020/V30/I05/386

［1］Hodi FS, Lawrence D, Lezcano C, et al. Bevacizumab plus ipilimumab in patients with metastatic melanoma\[J\]. Cancer Immunol Res, 2014, 2(7):632-642.

［2］Chen L, Han X. AntiPD1/PDL1 therapy of human cancer: past, present, and future\[J\]. J Clin Invest,2015,125(9):3384-3391.

［3］Herbst RS, Soria JC, Kowanetz M, et al. Predictive correlates of response to the antiPDL1 antibody MPDL3280A in cancer patients\[J\]. Nature,2014,515(7528):563-567.

［4］Brahmer JR, Tykodi SS, Chow LQ, et al. Safety and activity of antiPDL1 antibody in patients with advanced cancer\[J\]. N Engl J Med,2012,366(26):2455-2465.

［5］Anagnostou V, Smith KN, Forde PM, et al. Evolution of neoantigen landscape during immune checkpoint blockade in nonsmall cell lung cancer\[J\] Cancer Discov, 2017,7(3):264-276.

［6］Spigel DR, Schrock AB, Fabrizio D, et al. Total mutation burden (TMB) in lung cancer (LC) and relationship with response to PD1/PDL1 targeted therapies\[J\]. J Clin Oncol, 2016,34(15):9017.

［7］Borghaei H, Brahmer J. Nivolumab in nonsquamous nonsmallcell lung cancer\[J\]. N Engl J Med,2016,374(5):493-494.

［8］Fehrenbacher L, Spira A, Ballinger M, et al. Atezolizumab versus docetaxel for patients with previously treated nonsmallcell lung cancer (POPLAR): a multicentre, openlabel, phase 2 randomised controlled trial\[J\]. Lancet, 2016, 387(10030):1837-1846.

［9］Topalian SL, Hodi FS, Brahmer JR, et al. Safety, activity, and immune correlates of antiPD1 antibody in cancer\[J\]. N Engl J Med,2012,366(26):2443-2454.

［10］Vitale SG, Lagan AS, Capriglione S, et al. Target therapies for uterine carcinosarcomas: current evidence and future perspectives\[J\]. Int J Mol Sci, 2017, 18(5):1100.

［11］Chen DS, Mellman I. Oncology meets immunology: the cancerimmunity cycle\[J\]. Immunity, 2013, 39(1):1-10.

［12］Wolchok JD, Kluger H, Callahan MK, et al. Nivolumab plus ipilimumab in advanced melanoma\[J\]. N Engl J Med, 2013, 369(2):122-133.

［13］McGranahan N, Furness AJ, Rosenthal R, et al. Clonal neoantigens elicit T cell immunoreactivity and sensitivity to immune checkpoint blockade\[J\]. Science, 2016, 351(6280):1463-1469.

［14］Reck M, Bondarenko I, Luft A, et al. Ipilimumab in combination with paclitaxel and carboplatin as firstline therapy in extensivediseasesmallcell lung cancer: results from a randomized, doubleblind, multicenter phase 2 trial\[J\]. Ann Oncol, 2013, 24(1):75-83.

［15］Choudhury N, Nakamura Y. Importance of immunopharmacogenomics in cancer treatment: Patient selection and monitoring for immune checkpoint antibodies\[J\]. Cancer Sci, 2016, 107(2):107-115.

［16］Schumacher TN, Scheper W. A liquid biopsy for cancer immunotherapy\[J\]. Nat Med, 2016, 22(4):340-341.

［17］Heitzer E, Ulz P, Geigl JB. Circulating tumor DNA as a liquid biopsy for cancer\[J\]. Clin Chem,2015,61(1):112-123.

［18］Cheng F, Su L, Qian C. Circulating tumor DNA: a promising biomarker in the liquid biopsy of cancer\[J\]. Oncotarget,2016,7(30):48832-48841.

［19］Inoue H, Park JH, Kiyotani K, et al. Intratumoral expression levels of PDL1, GZMA, and HLAA along with oligoclonal T cell expansion associate with response to nivolumab in metastatic melanoma\[J\]. Oncoimmunology, 2016,5(9):e1204507.

［20］Shukuya T, Carbone DP. Predictive markers for the efficacy of antiPD1/PDL1 antibodies in lung cancer\[J\]. J Thorac Oncol, 2016,11(7):976-988.

［21］Larkin J, ChiarionSileni V, Gonzalez R, et al. Combined nivolumab and ipilimumab or monotherapy in untreated melanoma\[J\]. N Engl J Med,2015,373(1):23-34.

［22］Hegde PS, Karanikas V, Evers S. The where, the when, and the how of immune monitoring for cancer immunotherapies in the era of checkpoint inhibition\[J\]. Clin Cancer Res, 2016,22(8):1865-1874.

［23］Alexandrov LB, NikZainal S, Wedge DC, et al. Signatures of mutational processes in human cancer\[J\]. Nature, 2013,500(7463):415-421.

［24］Teng MW, Ngiow SF, Ribas A, et al. Classifying cancers based on Tcell infiltration and PDL1\[J\]. Cancer Res,2015,75(11):2139-2145.

［25］Smyth MJ, Ngiow SF, Ribas A, et al. Combination cancer immunotherapies tailored to the tumour microenvironment\[J\]. Nat Rev Clin Oncol, 2016,13(3):143-158.

［26］Konishi J, Yamazaki K, Azuma M, et al. B7H1 expression on nonsmall cell lung cancer cells and its relationship with tumorinfiltrating lymphocytes and their PD1 expression\[J\]. Clin Cancer Res, 2004,10(15):5094-5100.

［27］He Y, Yu H, Rozeboom L, et al. LAG3 Protein expression in nonsmall cell lung cancer and its relationship with PD1/PDL1 and tumorinfiltrating lymphocytes\[J\]. J Thorac Oncol, 2017, 12(5): 814-823.

［28］Zhang Y, Cai P, Liang T, et al. TIM3 is a potential prognostic marker for patients with solid tumors: A systematic review and metaanalysis\[J\]. Oncotarget, 2017,8(19):31705-31713.

［29］Liu XG, Hou M, Liu Y. TIGIT, a novel therapeutic target for tumor immunotherapy\[J\]. Immunol Invest, 2017,46(2):172-182.

［30］Koyama S, Akbay EA, Li YY, et al. Adaptive resistance to therapeutic PD1 blockade is associated with upregulation of alternative immune checkpoints\[J\]. Nat Commun,2016,7:10501.

［31］Inoue H, Park JH, Kiyotani K, et al. Intratumoral expression levels of PDL1, GZMA, and HLAA along with oligoclonal T cell expansion associate with response to nivolumab in metastatic melanoma\[J\]. Oncoimmunology, 2016,5(9):e1204507.

［32］Gros A, Parkhurst MR, Tran E, et al. Prospective identification of neoantigenspecific lymphocytes in the peripheral blood of melanoma patients\[J\]. Nat Med, 2016,22(4):433-438.

［33］Powles T, Eder JP, Fine GD, et al. MPDL3280A (antiPDL1) treatment leads to clinical activity in metastatic bladder cancer\[J\]. Nature,2014,515(7528):558-562.

［34］Rosenberg SA, Restifo NP. Adoptive cell transfer as personalized immunotherapy for human cancer\[J\]. Science, 2015,348(6230):62-68.

［35］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.

［36］Borghaei H, PazAres L, Horn L, et al. Nivolumab versus docetaxel in advanced nonsquamousnonsmallcell lung cancer\[J\]. N Engl J Med,2015,373(17):1627-1639.

［37］Khodadoust MS, Olsson N, Wagar LE, et al. Antigen presentation profiling reveals recognition of lymphoma immunoglobulin neoantigens\[J\]. Nature, 2017,543(7647):723-727.

［38］Zhang Y, Ma JA, Zhang Hx, et al. Cancer vaccines: Targeting KRASdriven cancer［J］. Expert Rev Vaccines, 2020,19(2):163-173.

［39］Cai LL, Ye HM, Zheng LM, et al. Circulating tumor cells(CTCs) as a liquid biopsy material and drug target\[J\]. Curr Drug Targets, 2014,15(10):965-972.

［40］Motzer RJ, Escudier B, McDermott DF, et al. Nivolumab versus everolimusinedvancedrenalcell carcinoma\[J\]. N Engl J Med, 2015,373(19):1803-1813.