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The tumor microenvironment (TME) plays a key\u00a0role in cancer progression and immune modulation, critically influencing the efficacy of ICIs. Recent advances in single\u2010cell technologies have enabled high\u2010resolution profiling of the TME, particularly tumor\u2010infiltrating immune cells, across diverse cancer types. However, our understanding of how immune cells shape ICI responses and how they are dynamically altered during treatment remains incomplete. In this review, we summarize recent progress in characterizing TME features associated with ICI responsiveness, highlighting key immune cell subsets involved in ICI therapy and emphasizing their phenotypic plasticity and functional adaptability following ICIs. Additionally, we outline the spatial architecture of the TME in terms of its effects on immune cell behavior and interactions, and discuss the critical role of stromal components and the microbiota in modulating the immune landscape and influencing ICI responsiveness. By integrating these insights, we aim to deepen our understanding of the cellular and molecular mechanisms underlying ICI responses, elucidate determinants of therapeutic sensitivity and resistance, and inform the development of more effective immunotherapeutic strategies.<\/jats:p>","DOI":"10.1002\/advs.202508692","type":"journal-article","created":{"date-parts":[[2025,8,28]],"date-time":"2025-08-28T10:16:12Z","timestamp":1756376172000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Insights into the Mechanisms of Immune\u2010Checkpoint Inhibitors Gained from Spatiotemporal Dynamics of the Tumor Microenvironment"],"prefix":"10.1002","volume":"12","author":[{"given":"Yuanyuan","family":"Zhang","sequence":"first","affiliation":[{"name":"State Key Laboratory of Molecular Oncology National Cancer Center\/National Clinical Research Center for Cancer\/Cancer Hospital Chinese Academy of Medical Sciences and Peking Union Medical College  Beijing 100021 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4242-033X","authenticated-orcid":false,"given":"Zhihua","family":"Liu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Molecular Oncology National Cancer Center\/National Clinical Research Center for Cancer\/Cancer Hospital Chinese Academy of Medical Sciences and Peking Union Medical College  Beijing 100021 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