{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T22:36:09Z","timestamp":1790634969109,"version":"4.1.0"},"reference-count":77,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T00:00:00Z","timestamp":1787184000000},"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>\n                    Laryngeal squamous cell carcinoma (LSCC) remains a clinically challenging malignancy of the head and neck. Because organ preservation is a major therapeutic objective in LSCC, stromal biology is of particular clinical relevance. Stromal factors influence local disease control, functional outcomes, and treatment resistance. Cancer-associated fibroblasts (CAFs) are dynamic regulators of extracellular matrix remodeling, immune exclusion, angiogenesis, and therapeutic resistance. However, LSCC-specific evidence remains fragmented, and many mechanistic concepts are still extrapolated from head and neck squamous cell carcinoma (HNSCC) and hypopharyngeal squamous cell carcinoma (HPSCC). This review adopts an evidence-stratified framework that distinguishes direct LSCC evidence from translatable cross-site evidence and hypothesis-generating inferences. We propose a provisional five-state model for LSCC that includes myofibroblastic, inflammatory, antigen-presenting, extracellular matrix-remodeling, and putative immune-trapping CAF programs. Direct LSCC studies support the presence of early stromal activation along the leukoplakia-to-carcinoma continuum and the enrichment of\n                    <jats:italic>FAP<\/jats:italic>\n                    -positive and\n                    <jats:italic>POSTN<\/jats:italic>\n                    -positive fibroblastic programs in metastatic disease. Associations involving stromal PD-L1 expression and altered CAF-derived exosomal microRNA cargo have also been reported. Translatable evidence from HNSCC implicates TGF-\u03b2- and CXCL12-dependent T-cell exclusion together with Gal9-mediated T-cell dysfunction. Additional mechanisms include IL-6\/JAK\/STAT3-driven myeloid skewing and NOX4-dependent stabilization of the myofibroblastic phenotype. We integrate these findings into a spatially informed conceptual framework encompassing the invasive front, the perivascular compartment, the cartilage interface, and the lymphovascular niche. We also discuss biomarker-guided therapeutic opportunities, including CAF normalization,\n                    <jats:italic>FAP<\/jats:italic>\n                    -directed approaches, stromal signaling blockade, extracellular matrix-targeted strategies, and interference with extracellular vesicle-mediated signaling. This review thereby establishes an evidence-stratified framework for CAF heterogeneity in LSCC and clarifies the translational value and current limitations of stroma-targeted strategies. It further provides a structured foundation for hypothesis-driven clinical and experimental investigation in laryngeal cancer.\n                  <\/jats:p>","DOI":"10.3389\/fimmu.2026.1848015","type":"journal-article","created":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T11:32:41Z","timestamp":1787225561000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Cancer-associated fibroblasts and immune remodeling in laryngeal squamous cell carcinoma: evidence and translational perspectives"],"prefix":"10.3389","volume":"17","author":[{"given":"Wei-Zhe","family":"Hong","sequence":"first","affiliation":[{"name":"Department of Otorhinolaryngology Head and Neck Surgery, Zhongshan Hospital of Traditional Chinese Medicine, Affiliated to Guangzhou University of Traditional Chinese Medicine","place":["Zhongshan, Guangdong, China"]},{"name":"The Tenth Clinical Medical College of Guangzhou University of Traditional Chinese Medicine","place":["Zhongshan, Guangdong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guan-Jiang","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology Head and Neck Surgery, Zhongshan Hospital of Traditional Chinese Medicine, Affiliated to Guangzhou University of Traditional Chinese Medicine","place":["Zhongshan, Guangdong, China"]},{"name":"The Tenth Clinical Medical College of Guangzhou University of Traditional Chinese Medicine","place":["Zhongshan, Guangdong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qi-Ping","family":"Luo","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology Head and Neck Surgery, Zhongshan Hospital of Traditional Chinese Medicine, Affiliated to Guangzhou University of Traditional Chinese Medicine","place":["Zhongshan, Guangdong, China"]},{"name":"The Tenth Clinical Medical College of Guangzhou University of Traditional Chinese 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