{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T22:36:50Z","timestamp":1790635010213,"version":"4.1.0"},"reference-count":43,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T00:00:00Z","timestamp":1786924800000},"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>Laryngeal squamous cell carcinoma (LSCC) shows a persistently low objective response rate to immune checkpoint inhibitors (ICIs) targeting the programmed death-1 (PD-1) pathway. Its immunosuppressive tumor microenvironment (TME), enriched in tumor-associated macrophages, immunosuppressive tumor-associated neutrophils (TANs), and regulatory T cells, is a principal driver of ICI failure. Yet one myeloid population central to ICI resistance across many malignancies has received no dedicated attention in this disease. Myeloid-derived suppressor cells (MDSCs) are heterogeneous, pathologically activated immature myeloid progenitors that suppress CD8+ T cell and natural killer cell cytotoxicity, promote regulatory T cell expansion, and sustain PD-1 blockade resistance through redundant mechanisms. In LSCC, tumor-derived G-CSF and GM-CSF activate the PI3K-AKT pathway in infiltrating neutrophils and upregulate PD-L1, and this same cytokine axis is an established upstream driver of MDSC differentiation and mobilization. The predominantly elderly, male, HPV-negative, tobacco-exposed patient profile further favors MDSC accumulation through aging-associated myeloid bias, senescence-associated secretory phenotype signaling, and chronic inflammation. Evidence support MDSCs as a clinically tractable immunosuppressive node in LSCC. These are the LSCC tumor secretome, the shared transcriptional landscape of polymorphonuclear MDSCs (PMN-MDSCs) and immunosuppressive TANs, and the clinical validation of circulating LOX-1+ PMN-MDSCs as predictors of ICI resistance in head and neck squamous cell carcinoma (HNSCC). Drawing on this evidence, we outline a mechanistic rationale connecting LSCC biology to MDSC expansion and argue that combining MDSC-targeting strategies with PD-1 blockade merits dedicated clinical investigation in this disease.<\/jats:p>","DOI":"10.3389\/fimmu.2026.1931000","type":"journal-article","created":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T05:25:38Z","timestamp":1786944338000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Myeloid-derived suppressor cells in laryngeal squamous cell carcinoma: an underexplored immunosuppressive axis and strategic target for overcoming checkpoint inhibitor resistance"],"prefix":"10.3389","volume":"17","author":[{"given":"Guan-Jiang","family":"Huang","sequence":"first","affiliation":[{"name":"Department of Otorhinolaryngology Head and Neck Surgery, Zhongshan Hospital of Traditional Chinese Medicine, Affiliated to Guangzhou University of Chinese 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