Zou Weiping, Wolchok Jedd D, Chen Lieping
Department of Surgery, University of Michigan School of Medicine, Ann Arbor, MI 48109, USA.
Department of Medicine and the Ludwig Center, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
Sci Transl Med. 2016 Mar 2;8(328):328rv4. doi: 10.1126/scitranslmed.aad7118.
PD-L1 and PD-1 (PD) pathway blockade is a highly promising therapy and has elicited durable antitumor responses and long-term remissions in a subset of patients with a broad spectrum of cancers. How to improve, widen, and predict the clinical response to anti-PD therapy is a central theme in the field of cancer immunology and immunotherapy. Oncologic, immunologic, genetic, and biological studies focused on the human cancer microenvironment have yielded substantial insight into this issue. Here, we focus on tumor microenvironment and evaluate several potential therapeutic response markers including the PD-L1 and PD-1 expression pattern, genetic mutations within cancer cells and neoantigens, cancer epigenetics and effector T cell landscape, and microbiota. We further clarify the mechanisms of action of these markers and their roles in shaping, being shaped, and/or predicting therapeutic responses. We also discuss a variety of combinations with PD pathway blockade and their scientific rationales for cancer treatment.
程序性死亡配体1（PD-L1）和程序性死亡受体1（PD-1）通路阻断是一种极具前景的治疗方法，已在多种癌症患者亚组中引发持久的抗肿瘤反应和长期缓解。如何改善、扩大和预测抗PD治疗的临床反应是癌症免疫学和免疫治疗领域的核心主题。针对人类癌症微环境的肿瘤学、免疫学、遗传学和生物学研究已对该问题有了深入了解。在此，我们聚焦于肿瘤微环境，评估几种潜在的治疗反应标志物，包括PD-L1和PD-1表达模式、癌细胞内的基因突变和新抗原、癌症表观遗传学和效应T细胞格局以及微生物群。我们进一步阐明这些标志物的作用机制及其在塑造、被塑造和/或预测治疗反应中的作用。我们还讨论了与PD通路阻断的各种联合应用及其用于癌症治疗的科学原理。
