{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,1]],"date-time":"2026-11-01T11:56:30Z","timestamp":1793534190627,"version":"4.5.0"},"reference-count":114,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,10,1]],"date-time":"2025-10-01T00:00:00Z","timestamp":1759276800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>CD8<jats:sup>+<\/jats:sup> T lymphocytes are central effectors of anticancer immunity. Their abundance and spatial distribution within solid tumors are strongly correlated with patient prognosis and response to immune-checkpoint inhibitors (ICIs). Tumors have been categorized into \u201chot,\u201d \u201cexcluded,\u201d and \u201ccold\u201d types based on the infiltration patterns of CD8<jats:sup>+<\/jats:sup> T cells, which reflect the underlying immune contexture and therapeutic potential. However, many tumors remain resistant to T-cell infiltration, posing a significant barrier to immunotherapy. This review systematically outlines the seven critical steps of the Cancer-Immunity Cycle that govern CD8<jats:sup>+<\/jats:sup> T-cell infiltration: antigen release, antigen processing and presentation, T-cell priming, trafficking through the vasculature, tumor infiltration, target recognition, and cytolytic activity. At each step, tumor-intrinsic and microenvironmental barriers\u2014including low tumor mutational burden, defective antigen-presenting machinery, immunosuppressive cytokines (e.g., TGF-\u03b2, IL-10), abnormal vasculature, fibroblast-derived extracellular matrix, and inhibitory cell populations (e.g., Tregs, MDSCs, TAMs)\u2014can stall the immune response. We further discuss the roles of immune-checkpoint signaling, metabolic competition, and suppressive cell networks in shaping T-cell exhaustion and exclusion. Cutting-edge technologies\u2014such as single-cell RNA-sequencing, spatial transcriptomics, imaging mass cytometry, and TCR repertoire profiling\u2014have revealed spatial and functional heterogeneity within intratumoral CD8<jats:sup>+<\/jats:sup> T cells and informed the design of rational combination therapies. Understanding and targeting these barriers is critical for converting immune-cold tumors into immune-infiltrated, therapy-responsive states. We conclude with a perspective on the future of immunoengineering and immune-atlas integration to optimize CD8<jats:sup>+<\/jats:sup> T-cell\u2013based interventions in solid tumors.<\/jats:p>","DOI":"10.3389\/fimmu.2025.1661545","type":"journal-article","created":{"date-parts":[[2025,10,1]],"date-time":"2025-10-01T09:57:01Z","timestamp":1759312621000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":37,"title":["Infiltration characteristics and regulatory mechanisms of CD8+ T lymphocytes in solid tumors: spatial distribution, biological functions, and interactions with the immune microenvironment"],"prefix":"10.3389","volume":"16","author":[{"given":"Peng","family":"Ouyang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianhong","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao","family":"He","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Congcong","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dingcheng","family":"Zeng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daofeng","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,10,1]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1038\/s41568-020-0285-7","article-title":"The 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