Department of Radiation Oncology, Weill Cornell Medical College, New York, NY 10065, USA.
Sandra and Edward Meyer Cancer Center, New York, NY 10065, USA.
Sci Transl Med. 2018 Sep 19;10(459). doi: 10.1126/scitranslmed.aat7807.
Immunotherapy is revolutionizing the clinical management of multiple tumors. However, only a fraction of patients with cancer responds to immunotherapy, and currently available immunotherapeutic agents are expensive and generally associated with considerable toxicity, calling for the identification of robust predictive biomarkers. The overall genomic configuration of malignant cells, potentially favoring the emergence of immunogenic tumor neoantigens, as well as specific mutations that compromise the ability of the immune system to recognize or eradicate the disease have been associated with differential sensitivity to immunotherapy in preclinical and clinical settings. Along similar lines, the type, density, localization, and functional orientation of the immune infiltrate have a prominent impact on anticancer immunity, as do features of the tumor microenvironment linked to the vasculature and stroma, and systemic factors including the composition of the gut microbiota. On the basis of these considerations, we outline the hallmarks of successful anticancer immunotherapy.
免疫疗法正在彻底改变多种肿瘤的临床治疗模式。然而，只有一小部分癌症患者对免疫疗法有反应，并且目前可用的免疫治疗药物昂贵，通常与相当大的毒性有关，因此需要寻找强大的预测性生物标志物。恶性细胞的整体基因组结构，可能有利于免疫原性肿瘤新抗原的出现，以及特定的突变，这些突变会削弱免疫系统识别或消除疾病的能力，这些都与临床前和临床环境中对免疫疗法的不同敏感性有关。类似地，免疫浸润的类型、密度、定位和功能方向，以及与血管和基质相关的肿瘤微环境的特征，以及包括肠道微生物组组成在内的系统性因素，都对抗肿瘤免疫有显著影响。基于这些考虑，我们概述了成功的癌症免疫治疗的特征。
