小细胞肺癌的免疫特征

Immune Characteristics of Small Cell Lung Cancer

小细胞肺癌(small cell lung cancer, SCLC)是预后极差的一类肿瘤,30年来药物治疗无显著进展,免疫检查点抑制剂(immune checkpoint inhibitor, ICI)成为近年唯一突破:程序性死亡-1(programmed death-1, PD-1)抑制剂单药或联合细胞毒T淋巴细胞抗原-4(cytotoxic T-lymphocyte antigen-4, CTLA-4)抑制剂后线治疗SCLC的有效率为10%-33%,有效时间较持久;程序性死亡配体-1(programmed death ligand-1, PD-L1)抑制剂联合化疗对比传统化疗一线治疗广泛期SCLC(extensive stage-SCLC, ES-SCLC)的总生存期延长。尽管取得一定疗效,相对于非小细胞肺癌(non-small cell lung cancer, NSCLC)等对免疫治疗敏感的肿瘤类型,SCLC的疗效仍不令人满意,这可能与其免疫抑制特征有关。本综述对SCLC免疫特征的研究现状进行总结,包括淋巴细胞和免疫抑制细胞在肿瘤内浸润情况、PD-L1和主要组织相容复合物(major histocompatibility complex, MHC)在肿瘤的表达以及外周血免疫细胞的改变,并对这些免疫特征的预后及其对ICI疗效的预测价值进行分析。

Small cell lung cancer(SCLC) is a type of malignancy with poor prognosis, and no advance in medication has been made for about 30 years except immune checkpoint inhibitor(ICI), which demonstrated efficacy in recent years. The response rate of programmed death-1(PD-1) inhibitor alone or its combination with cytotoxic T-lymphocyte antigen-4(CTLA-4) inhibitor as subsequent therapy was 10%-33% and the response duration was persistent. The combination of programmed death ligand-1(PD-L1) inhibitor with chemotherapy resulted in longer survival versus chemotherapy alone. Nevertheless, comparing with immunotherapy-sensitive tumors such as non-small cell lung cancer(NSCLC), efficacy in SCLC is still unsatisfied and this is maybe associated with its immune inhibitory characteristics. This review describes the current research about immune characteristics of SCLC, including tumor infiltrating of lymphocytes(TIL) and immune inhibitory cells, PD-L1 and major histocompatibility complex(MHC) expression in tumor as well as changes of peripheral immune cells. We also review the prognostic and predictive values of these immune characteristics.