Immunotherapy has prompted a paradigm shift in advanced non-small cell lung cancer (NSCLC) treatment, by demonstrating superior efficacy to chemotherapy alone both in second- and in first-line setting. Novel insights on molecular mechanisms and regimens to enhance the efficacy of immunotherapy are warranted, as only a minority of patients (˜20%) respond to checkpoint blockade. Taking into account the multiple mechanisms adopted by tumor cells to evade the immune system through cancer immunoediting, the frontline combination of immune checkpoint inhibitors with chemotherapy appears to be a successful strategy as: 1) it enhances the recognition and elimination of tumor cells by the host immune system (immunogenic cell-death), and 2) it reduces the immunosuppressive tumor microenvironment. Remarkably, the immune checkpoint inhibitors pembrolizumab and atezolizumab have already been approved by the FDA in combination with chemotherapy for the first-line treatment of advanced NSCLC and many other chemo-immunotherapeutic regimens have been evaluated as an initial therapeutic approach in metastatic NSCLC. Concurrently, several preclinical studies are evaluating the molecular mechanisms underlying immunomodulation by conventional chemotherapeutic agents (platinum salts, antimitotic agents, antimetabolites and anthracyclines), unraveling drug- and dose/schedule-dependent effects on the immune system that should be exploited to achieve synergistic clinical activity. The current review provides a detailed overview of the immunobiological rationale and molecular basis for combining immune checkpoint inhibitors with chemotherapy for the treatment of advanced NSCLC. Moreover, current evidence and future perspectives towards a better selection of patients who are more likely to benefit from chemo-immunotherapy combinations are discussed.

免疫疗法通过证明在二线和一线治疗中优于单纯化疗的疗效，已经促使晚期非小细胞肺癌（NSCLC）治疗发生了范例转变。由于只有少数患者（约20％）对检查站封锁有反应，因此有必要对提高免疫疗法功效的分子机制和方案进行新的见解。考虑到肿瘤细胞通过癌症免疫编辑逃避免疫系统所采用的多种机制，免疫检查点抑制剂与化学疗法的一线结合似乎是一个成功的策略，因为：1）它增强了宿主对肿瘤细胞的识别和清除能力免疫系统（免疫原性细胞死亡），以及2）降低免疫抑制肿瘤的微环境。值得注意的是 FDA已经批准了免疫检查点抑制剂pembrolizumab和atezolizumab联合化疗用于晚期NSCLC的一线治疗，并且许多其他化学免疫治疗方案已被评估为转移性NSCLC的初始治疗方法。同时，一些临床前研究正在评估通过常规化学治疗剂（铂盐，抗有丝分裂剂，抗代谢药和蒽环类药物）进行免疫调节的分子机制，阐明对免疫系统的药物和剂量/时间表依赖性作用，应利用这些作用来实现协同临床效果活动。本综述提供了将免疫检查点抑制剂与化学疗法联合用于治疗晚期NSCLC的免疫生物学原理和分子基础的详细概述。此外，讨论了更好地选择更可能受益于化学免疫疗法组合的患者的当前证据和未来观点。