生物标志物在阻断PD-1/PD-L1通路治疗肿瘤中的预测性作用

doi:10.3760/cma.j.issn.1673-422X.2016.06.014

国际肿瘤学杂志 ›› 2016, Vol. 43 ›› Issue (6): 452-454.doi: 10.3760/cma.j.issn.1673-422X.2016.06.014

生物标志物在阻断PD-1/PD-L1通路治疗肿瘤中的预测性作用

崔金元，陶凯雄

430022 武汉，华中科技大学同济医学院附属协和医院胃肠外科

收稿日期:2015-11-09 出版日期:2016-06-08 发布日期:2016-04-27
通讯作者: 陶凯雄 E-mail:tao_kaixiong@163.com
基金资助:
国家自然科学基金（81572413）

Predictive biomarkers in tumor treatment by blocking PD-1/PD-L1 pathway

Cui Jinyuan, Tao Kaixiong

Department of Gastrointestinal Surgery, Wuhan Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China

Received:2015-11-09 Online:2016-06-08 Published:2016-04-27
Contact: Tao Kaixiong E-mail:tao_kaixiong@163.com
Supported by:
National Natural Science Foundation of China (81572413)

摘要/Abstract

摘要： 确定预测PD-1/PD-L1通路阻断治疗临床反应的生物标志物有助于患者筛查和个体化治疗。研究证明治疗前肿瘤组织中肿瘤细胞和肿瘤浸润淋巴细胞PDL1的高表达，肿瘤间CD8+T细胞的大量浸润以及肿瘤细胞基因高突变负荷的患者阻断PD-1/PD-L1通路治疗的临床疗效更明显，这些生物标志物有望成为筛查肿瘤患者的指标。

关键词: 肿瘤, 治疗, 生物学标记, PD-1/PD-L1通路

Abstract: Identifying biomarkers predicting clinical response to treatment of PD1/PDL1 pathway blockade can guide patient selection and therapeutic individualization. Some researches have shown that patients with cancer will acquire better clinical effects by blocking PD-1/PD-L1 pathway whose characteristics include higher pretreatment expression of PD-L1 by tumor cells or tumor infiltrating immune cells, the massive infiltration of intratumoral CD8+ T cells, the high mutation frequency of tumor cell gene. These biomarkers are expected to become indicators which can select patients.

Key words: Neoplasms, Therapy, Biological markers, PD-1/PD-L1 pathway

崔金元，陶凯雄. 生物标志物在阻断PD-1/PD-L1通路治疗肿瘤中的预测性作用[J]. 国际肿瘤学杂志, 2016, 43(6): 452-454.

Cui Jinyuan, Tao Kaixiong. Predictive biomarkers in tumor treatment by blocking PD-1/PD-L1 pathway[J]. Journal of International Oncology, 2016, 43(6): 452-454.

参考文献

［1］ Postow MA, Callahan MK, Wolchok JD. Immune checkpoint blockade in cancer therapy［J］. J Clin Oncol, 2015, 33(17): 1974-1982. DOI: 10.1200/JCO.2014.59.4358.　［2］邵婧怡, 孙国平. 程序性死亡受体1及其配体在恶性肿瘤中的研究进展［J］. 国际肿瘤学杂志, 2015 (5): 358-360. DOI: 10.3760/cma.j.issn.1673422X.2015.05.010. ［3］ Keir ME, Butte MJ, Freeman GJ, et al. PD1 and its ligands in tolerance and immunity［J］. Annu Rev Immunol, 2008, 26: 677-704. DOI: 10.1146/annurev.immunol.26.021607.090331. ［4］施敏骅, 邢玉斐, 张增利, 等. 肺癌细胞中可溶性程序性死亡配体1的表达及其对T细胞功能的影响［J］. 中华肿瘤杂志, 2013, 35(2): 85-88. DOI: 10.3760/cma.j.issn.02533766.2013.02.002. ［5］ Taube JM, Anders RA, Young GD, et al. Colocalization of inflammatory response with B7h1 expression in human melanocytic lesions supports an adaptive resistance mechanism of immune escape［J］. Sci Transl Med, 2012, 4(127): 127ra37. DOI: 10.1126/scitranslmed.3003689. ［6］ Tumeh PC, Harview CL, Yearley JH, et al. PD1 blockade induces responses by inhibiting adaptive immune resistance［J］. Nature, 2014, 515(7528): 568-571. DOI: 10.1038/nature13954. ［7］ Dong H, Strome SE, Salomao DR, et al. Tumorassociated B7H1 promotes Tcell apoptosis: a potential mechanism of immune evasion［J］. Nat Med, 2002, 8(8): 793-800. DOI: 10.1038/nm730. ［8］ Azuma T, Yao S, Zhu GF, et al. B7H1 is a ubiquitous antiapoptotic receptor on cancer cells［J］. Blood, 2008, 111(7): 3635-3643. DOI: 10.1182/blood-2007-11-123141. ［9］ Yang Y, Wu KE, Zhao E, et al. B7H1 enhances proliferation ability of gastric cancer stemlike cells as a receptor［J］. Oncol Lett, 2015, 9(4): 18331838. DOI: 10.3892/ol.2015.2949. ［10］ Pardoll DM. The blockade of immune checkpoints in cancer immunotherapy［J］. Nat Rev Cancer, 2012, 12(4): 252-264. DOI: 10.1038/nrc3239. ［11］ 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. DOI: 10.1038/nature14011. ［12］ Philips GK, Atkins M. Therapeutic uses of antiPD1 and antiPDL1 antibodies［J］. Int Immunol, 2015, 27(1): 39-46. DOI: 10.1093/intimm/dxu095. ［13］ 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. DOI: 10.1056/NEJMoa1200694. ［14］ 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(33): 23-35. DOI: 10.1016/j.coi.2015.01.006. ［15］ 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. DOI: 10.1056/NEJMoa1200690. ［16］ Wolchok JD. PD-1 blockers［J］. Cell, 2015, 162(5): 937. DOI: 10.1016/j.cell.2015.07.045. ［17］ 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. DOI: 10.1038/nature13904. ［18］ Swaika A, Hammond WA, Joseph RW. Current state of antiPDL1 and antiPD1 agents in cancer therapy［J］. Mol Immunol, 2015, 67(2 Pt A): 4-17. DOI: 10.1016/j.molimm.2015.02.009. ［19］ Lote H, Cafferkey C, Chau I. PD1 and PDL1 blockade in gastrointestinal malignancies［J］. Cancer Treat Rev, 2015, 41(10): 893903. DOI: 10.1016/j.ctrv.2015.09.004. ［20］ Taube JM, Klein A, Brahmer JR, et al. Association of PD-1, PD-1 ligands, and other features of the tumor immune microenvironment with response to antiPD-1 therapy［J］. Clin Cancer Res, 2014, 20(19): 5064-5074. DOI: 10.1158/1078-0432.CCR-13-3271. ［21］ Atefi M, Avramis E, Lassen A, et al. Effects of MAPK and PI3K pathways on PDL1 expression in melanoma［J］. Clin Cancer Res, 2014, 20(13): 34463457. DOI: 10.1158/10780432.CCR132797. ［22］ Rech AJ, Vonderheide RH. Dynamic interplay of oncogenes and T cells induces PDL1 in the tumor microenvironment［J］. Cancer Discov, 2013, 3(12): 1330-1332. DOI: 10.1158/21598290.CD-13-0775. ［23］ Brahmer JR, Drake CG, Wollner I, et al. Phase Ⅰ study of singleagent antiprogrammed death1 (MDX1106) in refractory solid tumors: safety, clinical activity, pharmacodynamics, and immunologic correlates［J］. J Clin Oncol, 2010, 28(19): 3167-3175. DOI: 10.1200/JCO.2009.26.7609. ［24］ Lawrence MS, Stojanov P, Polak P, et al. Mutational heterogeneity in cancer and the search for new cancerassociated genes［J］. Nature, 2013, 499(7457): 214218. DOI: 10.1038/nature12213. ［25］ Gubin MM, Zhang X, Schuster H, et al. Checkpoint blockade cancer immunotherapy targets tumourspecific mutant antigens［J］. Nature, 2014, 515(7528): 577-581. DOI: 10.1038/nature13988. ［26］ Matsushita H, Vesely MD, Koboldt DC, et al. Cancer exome analysis reveals a Tcelldependent mechanism of cancer immunoediting［J］. Nature, 2012, 482(7385): 400-404. DOI: 10.1038/nature10755. ［27］ Fritsch EF, Rajasagi M, Ott PA, et al. HLAbinding properties of tumor neoepitopes in humans［J］. Cancer Immunol Res, 2014, 2(6): 522-529. DOI: 10.1158/2326-6066.CIR-13-0227. ［28］ Latchman Y, Wood CR, Chernova T, et al. PD-L2 is a second ligand for PD1 and inhibits T cell activation［J］. Nat Immunol, 2001, 2(3): 261-268. DOI: 10.1038/85330.

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生物标志物在阻断PD-1/PD-L1通路治疗肿瘤中的预测性作用

Predictive biomarkers in tumor treatment by blocking PD-1/PD-L1 pathway

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