Tumor and Host Factors Controlling Antitumor Immunity and Efficacy of Cancer Immunotherapy.
Tumor and Host Factors Controlling Antitumor Immunity and Efficacy of Cancer Immunotherapy.
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DOI：
10.1016/bs.ai.2015.12.003
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发表时间：
2016
影响因子：
--
通讯作者：
Gajewski TF
中科院分区：
文献类型：
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作者：
Spranger S;Sivan A;Corrales L;Gajewski TF
尽管最近在免疫治疗方面取得了临床进展，但一小部分癌症患者对这些干预措施没有反应。来自临床前小鼠模型以及临床样本的证据提供了证据，表明肿瘤微环境中活化T细胞浸润的程度与对免疫疗法（包括检查点阻断）的临床应答相关。因此，了解介导T细胞缺乏浸润到肿瘤微环境中的分子机制将有助于开发新的治疗策略，以使这些患者对免疫治疗有反应。最近的数据表明，受试者间异质性的主要来源包括个体受试者癌症之间特定癌基因通路中的体细胞突变差异以及环境因素（包括肠道微生物组成）。成功识别这些致病因素应该会导致新的治疗方法，可以促进T细胞进入非炎症肿瘤，并扩大能够对新型免疫疗法作出反应的患者比例。
Despite recent clinical advances in immunotherapy, a fraction of cancer patients fails to respond to these interventions. Evidence from preclinical mouse models as well as clinical samples has provided evidence that the extent of activated T cell infiltration within the tumor microenvironment is associated with clinical response to immunotherapies including checkpoint blockade. Therefore, understanding the molecular mechanisms mediating the lack of T cell infiltration into the tumor microenvironment will be instrumental for the development of new therapeutic strategies to render those patients immunotherapy responsive. Recent data have suggested that major sources of intersubject heterogeneity include differences in somatic mutations in specific oncogene pathways between cancers of individual subjects and also environmental factors including commensal microbial composition. Successful identification of such causal factors should lead to new therapeutic approaches that may facilitate T cell entry into noninflamed tumors and expand the fraction of patients capable of responding to novel immunotherapies.