{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T09:04:45Z","timestamp":1789635885761,"version":"4.0.0"},"reference-count":138,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T00:00:00Z","timestamp":1789603200000},"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>While immune checkpoint blockade (ICB) targeting PD-1 and CTLA-4 has revolutionized the treatment of skin cancers, a significant proportion of patients with advanced melanoma and cutaneous squamous cell carcinoma (cSCC) exhibit primary or acquired resistance. Identifying non-redundant inhibitory pathways is crucial for the next generation of immunotherapy. As a unique checkpoint, VISTA (PD-1H) maintains immune tolerance through a distinct pH-sensitive mechanism. In the acidic tumor microenvironment (TME), protonated histidine residues enhance VISTA\u2019s binding affinity, allowing it to act as a localized guardian of immune privilege in both melanoma and cutaneous squamous cell carcinoma. By integrating molecular insights with bioengineering innovations, VISTA-directed rational combinations demonstrate significant preclinical potential to overcome immune resistance and achieve durable responses in refractory malignancies.<\/jats:p>","DOI":"10.3389\/fimmu.2026.1815113","type":"journal-article","created":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T08:37:31Z","timestamp":1789634251000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Targeting VISTA as a novel immunotherapy for skin cancer"],"prefix":"10.3389","volume":"17","author":[{"given":"Yulong","family":"Hou","sequence":"first","affiliation":[{"name":"Huzhou Central Hospital, Fifth School of Clinical Medicine of Zhejiang Chinese Medical University","place":["Huzhou, China"]},{"name":"Huzhou Central Hospital, Affiliated Central Hospital of Huzhou University","place":["Huzhou, 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