Multi-dimensional characterization of immunological profiles in small cell lung cancer uncovers clinically relevant immune subtypes with distinct prognoses and therapeutic vulnerabilities

作者：Lin Yang, Zicheng Zhang, Jiyan Dong, Yibo Zhang, Zijian Yang, Yiying Guo, Xujie Sun, Junling Li, Puyuan Xing, Jianming Ying, Meng Zhou · 发表于：Pharmacological Research · 年份：2023 · DOI：10.1016/j.phrs.2023.106844 · 被引用次数：23 · 研究领域：Lung Cancer Research Studies、Neuroendocrine Tumor Research Advances、Lung Cancer Treatments and Mutations

Small-cell lung cancer (SCLC) is generally considered a 'homogenous' disease, with little documented inter-tumor heterogeneity in treatment guidance or prognosis evaluation. The precise identification of clinically relevant molecular subtypes remains incomplete and their translation into clinical practice is limited. In this retrospective cohort study, we comprehensively characterized the immune microenvironment in SCLC by integrating transcriptional and protein profiling of formalin-fixation-and-paraffin-embedded (FFPE) samples from 29 patients. We identified two distinct disease subtypes: immune-enriched (IE-subtype) and immune-deprived (ID-subtype), displaying heterogeneity in immunological, biological, and clinical features. The IE-subtype was characterized by abundant immune infiltrate and elevated levels of interferon-alpha/gamma (IFNα/IFNγ) and inflammatory response, while the ID-subtype featured a complete lack of immune infiltration and a more proliferative phenotype. These two immune subtypes are associated with clinical benefits in SCLC patients treated with adjuvant therapy, with the IE-subtype exhibiting a more favorable response leading to improved survival and reduced disease recurrence risk. Additionally, we identified and validated a personalized prognosticator of immunophenotyping, the CCL5/CXCL9 chemokine index (CCI), using machine learning. The CCI demonstrated superior predictive abilities for prognosis and clinical benefits in SCLC patients, validated in...