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Immunol."],"abstract":"<jats:p>Small cell lung cancer (SCLC) remains one of the most aggressive malignancies, characterized by limited therapeutic options and persistently poor survival outcomes. This review summarizes recent advances in understanding the immunosuppressive tumor microenvironment, emerging therapeutic strategies, and biomarker-driven approaches that may enable more precise treatment. The SCLC microenvironment is dominated by suppressive immune cell populations\u2014including regulatory T cells, tumor-associated macrophages, and myeloid-derived suppressor cells\u2014that collectively inhibit antitumor immune responses. Integrative molecular and immunologic profiling has defined four transcription factor\u2013driven subtypes, each exhibiting distinct immune phenotypes and differential responses to therapy. Although current immunotherapies have conferred meaningful yet modest clinical gains, combining PD-1\/PD-L1 blockade with chemotherapy has improved survival in extensive-stage disease, and CTLA-4 inhibition demonstrates potential within combination regimens. Beyond immune checkpoint blockade, novel therapeutic modalities such as DLL3-targeted antibody\u2013drug conjugates, bispecific T-cell engagers, and emerging B7-H3\u2013directed strategies have shown encouraging activity in treatment-refractory settings. However, conventional biomarkers\u2014including PD-L1 expression and tumor mutational burden\u2014remain unreliable in SCLC, and the mechanisms underlying therapeutic resistance are still insufficiently understood. Future efforts should prioritize the refinement of molecular subtyping frameworks, the establishment of robust biomarker-guided patient stratification, the elucidation of resistance pathways, and the development of precision immunotherapies tailored to SCLC heterogeneity.<\/jats:p>","DOI":"10.3389\/fimmu.2026.1765497","type":"journal-article","created":{"date-parts":[[2026,3,11]],"date-time":"2026-03-11T06:50:29Z","timestamp":1773211829000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["Small cell lung cancer: from immunobiological mechanisms to clinical advances"],"prefix":"10.3389","volume":"17","author":[{"given":"Xian","family":"Zhong","sequence":"first","affiliation":[{"name":"Department of Medical Oncology, the Second Affiliated Hospital, Zhejiang University School of Medicine","place":["Hangzhou, Zhejiang, China"]},{"name":"Cancer Institute (Key Laboratory of Cancer Prevention and Intervention, Chinese 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