生物标志物驱动的小细胞肺癌免疫检查点抑制剂治疗见解

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生物标志物驱动的小细胞肺癌免疫检查点抑制剂治疗见解

英文原题：Biomarker-driven insights into immune checkpoint inhibitor therapy in small-cell lung cancer.

PubMed 2026/08/06（内容时间） Crit Rev Oncol Hematol Q1 · IF 6.2（JCR 2025）

小细胞肺癌地区：中国

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研究概要

小细胞肺癌（SCLC）是一种侵袭性恶性肿瘤，治疗选择有限，而将免疫检查点抑制剂（ICIs）纳入治疗方案已重塑了治疗格局。

中文摘要

小细胞肺癌（SCLC）是一种侵袭性恶性肿瘤，治疗选择有限，免疫检查点抑制剂（ICIs）纳入治疗方案已重塑了治疗格局。然而，快速耐药和缺乏有效预测性生物标志物等挑战仍然存在。本综述重点阐述了生物标志物在 SCLC 中的关键作用，强调了它们在肿瘤内在机制、肿瘤微环境（TME）免疫景观和全身宿主因素方面对治疗耐药的贡献。肿瘤内在特征，包括分子亚型、TP53 和 RB1 突变等基因改变以及肿瘤突变负荷（TMB），已显示出与 ICI 疗效的不同关联。值得注意的是，SCLC-I（炎症型）分子亚型似乎对免疫治疗更敏感。在 TME 中，程序性细胞死亡配体 1 表达、TIL（肿瘤浸润淋巴细胞）（TILs）、调节性 T 细胞、髓源性抑制细胞以及组织相关细胞因子和趋化因子参与免疫调节。高 CD8+ TILs 与更好的预后相关，而免疫抑制性细胞群增加通常会抑制抗肿瘤反应。全身因素，包括肿瘤来源成分（ctDNA、CTCs、肿瘤来源 EVs）和宿主来源成分（循环免疫细胞表型、MHC 表达、免疫特征、基线临床特征）以及心理因素，为治疗反应和预后提供了有价值的见解。需要进一步研究来验证生物标志物并探索克服耐药的联合方案，为改善 SCLC 患者预后带来希望。

展开英文摘要原文

Small cell lung cancer (SCLC) is an aggressive malignancy with limited treatment options, and the integration of immune checkpoint inhibitors (ICIs) into treatment regimens has reshaped the therapeutic landscape. However, challenges such as rapid resistance and lack of effective predictive biomarkers remain. This review highlights the pivotal roles of biomarkers in SCLC, underscoring their contributions to treatment resistance across tumor-intrinsic mechanisms, immune landscape of the tumor microenvironment (TME) and systemic host factors. Tumor-intrinsic features, including molecular subtypes, genetic alterations such as TP53 and RB1 mutations, and tumor mutation burden (TMB), have shown varying associations with ICI efficacy. Notably, the SCLC-I (inflamed) molecular subtype appears more responsive to immunotherapy. Within the TME, programmed cell death ligand 1 expression, tumor-infiltrating lymphocytes (TILs), regulatory T cells, myeloid-derived suppressor cells, and tissue-associated cytokines and chemokines contribute to immune modulation. High CD8 + TILs are linked to better outcomes, while increased immunosuppressive populations often suppress anti-tumor response. Systemic factors, encompassing tumor-derived (ctDNA, CTCs, tumor-derived EVs) and host-derived (circulating immune cell phenotypes, MHC expression, immune profile, baseline clinical characteristics) components, and psychological factors, provide valuable insights into treatment response and prognosis. Further research is needed to validate biomarkers and investigate combination approaches to overcome resistance, offering hope for improved patient outcomes in SCLC.

论文信息

作者: Wang S、Zhao X、Zeng Y、Li W、Huang J、Leung EL、Png S、Liang A
第一作者单位: Department of Oncology, The Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, China; Xiangya School of Medicine, Central South University, Changsha, Hunan 410013, China.China
通讯作者单位: Department of Oncology, The Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, China; Hunan Cancer Mega-Data Intelligent Application and Engineering Research Centre, China; Changsha Thoracic Cancer Prevention and Treatment Technology Innovation Center, Changsha, Hunan, China; Hunan Key Laboratory of Tumor Models and Individualized Medicine, The Second Xiangya Hospital, Central South University, The Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, China; Hunan Key Laboratory of Early Diagnosis and Precision Therapy in Lung Cancer, The Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, China; FuRong Laboratory, Changsha, Hunan 410078, China. Electronic address: wufang4461@csu.edu.cn.China
文献类型: 综述
期刊: Critical reviews in oncology/hematology2026 Aug 6

原文标识: PubMed 42562245　·　DOI 10.1016/j.critrevonc.2026.105517

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