{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T11:20:54Z","timestamp":1787570454175,"version":"build-2736575974"},"reference-count":249,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T00:00:00Z","timestamp":1787529600000},"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>Tumor microenvironment-resident immunosuppressive cells-comprising myeloid-derived suppressor cells, regulatory T cells, and tumor-associated macrophages-constitute primary obstacles to effective cancer immunotherapy. Advances in single-cell and spatial multi-omics have uncovered their substantial functional heterogeneity, tissue-adaptive reprogramming, and organ-specific architectures distinguishing primary tumors from metastatic lesions. Beyond canonical immune checkpoint pathways, non-canonical regulatory layers--including metabolic-immune crosstalk, epigenetic regulation, microbiome-mediated distant signaling, and therapy-induced adaptive remodeling-further reinforce treatment resistance. Based on these mechanistic insights, systematic synergistic strategies have been developed, such as multi-pathway checkpoint blockade, ADC-immunotherapy combinations, temporally and spatially optimized conventional therapies, and targeted agents that deplete or reprogram suppressive populations. Emerging biomarkers, repurposed pharmaceuticals, and pan-cancer therapeutic principles are refining patient stratification and combination regimens. This review offers a comprehensive framework for understanding and surmounting immunosuppressive barriers in cancer therapy.<\/jats:p>","DOI":"10.3389\/fimmu.2026.1896156","type":"journal-article","created":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T10:32:49Z","timestamp":1787567569000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Immunosuppressive cells as barriers to cancer therapy: mechanisms and emerging solutions"],"prefix":"10.3389","volume":"17","author":[{"given":"Mengmeng","family":"Liu","sequence":"first","affiliation":[{"name":"Department of Integrated Chinese and Western Medicine, Affiliated Cancer Hospital of Zhengzhou University and Henan Cancer Hospital","place":["Zhengzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yichen","family":"Zhu","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Affiliated Cancer Hospital of Zhengzhou 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