{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T00:49:17Z","timestamp":1790124557481,"version":"4.0.1"},"reference-count":28,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,6,26]],"date-time":"2025-06-26T00:00:00Z","timestamp":1750896000000},"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:sec><jats:title>Introduction<\/jats:title><jats:p>Immune checkpoint inhibitors (ICIs) have transformed the therapeutic landscape of malignant melanoma; however, they are frequently associated with immune-related adverse events (irAEs). Emerging evidence suggests that genetic predispositions, including interleukin-7 (IL-7) gene variants, may influence the risk of these toxicities.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>In this single-center retrospective study, we investigated the potential utility of IL-7 rs16906115 polymorphism and lymphocyte stability index (LSI) in predicting susceptibility to irAEs among 96 melanoma patients treated with ICIs.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Genotyping revealed a minor allele frequency of 8.3% for rs16906115. Logistic regression analysis indicated that carriers of the minor allele had a significantly increased risk of all-grade irAEs compared to reference allele carriers (adjusted OR: 3.93; 95%CI:1.13\u201313.64; p=0.031). Subgroup analyses revealed a significant increase in risk across endocrine, non-cutaneous, multiple, low-grade, and early onset (&amp;lt;3 months) irAEs. While neither baseline lymphocyte count nor LSI predicted overall irAE incidence, an elevated LSI emerged as a key risk factor for early steroid-requiring irAEs (adjusted OR:3.79; 95% CI: 1.14\u201312.61; p =0.030).<\/jats:p><\/jats:sec><jats:sec><jats:title>Discussion<\/jats:title><jats:p>These findings from a Turkish cohort corroborate earlier European studies suggesting that rs16906115 minor allele carriage may be a genetic risk factor for irAEs. Furthermore, LSI may serve as a dynamic biomarker for predicting early steroid-requiring irAEs. Prospective multicenter studies among diverse populations are warranted to validate these findings.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fimmu.2025.1616325","type":"journal-article","created":{"date-parts":[[2025,6,26]],"date-time":"2025-06-26T04:10:16Z","timestamp":1750911016000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":9,"title":["Predicting immune-related adverse events in patients with melanoma: the role of interleukin-7 rs16906115 polymorphism and lymphocyte dynamics"],"prefix":"10.3389","volume":"16","author":[{"given":"Fatma 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