Predicting immune-related adverse events in patients with melanoma: the role of interleukin-7 rs16906115 polymorphism and lymphocyte dynamics
IntroductionImmune 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,...
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Frontiers Media S.A.
2025-06-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2025.1616325/full |
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| author | Fatma Pınar Açar Caner Acar Damla Gunenc Çağlar Arisoy Asli Ece Solmaz Asli Gecgel Haydar Çağatay Yüksel Gökhan Şahin Oguzcan Ozkan Zeynep Sila Gokdere Nilay Duman Burçak Karaca |
| author_facet | Fatma Pınar Açar Caner Acar Damla Gunenc Çağlar Arisoy Asli Ece Solmaz Asli Gecgel Haydar Çağatay Yüksel Gökhan Şahin Oguzcan Ozkan Zeynep Sila Gokdere Nilay Duman Burçak Karaca |
| author_sort | Fatma Pınar Açar |
| collection | DOAJ |
| description | IntroductionImmune 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.MethodsIn 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.ResultsGenotyping 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:1.13–13.64; p=0.031). Subgroup analyses revealed a significant increase in risk across endocrine, non-cutaneous, multiple, low-grade, and early onset (<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: 1.14–12.61; p =0.030).DiscussionThese 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. |
| format | Article |
| id | doaj-art-23bd183d5e334f63b174df6e1345da12 |
| institution | Kabale University |
| issn | 1664-3224 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj-art-23bd183d5e334f63b174df6e1345da122025-08-20T03:30:35ZengFrontiers Media S.A.Frontiers in Immunology1664-32242025-06-011610.3389/fimmu.2025.16163251616325Predicting immune-related adverse events in patients with melanoma: the role of interleukin-7 rs16906115 polymorphism and lymphocyte dynamicsFatma Pınar Açar0Caner Acar1Damla Gunenc2Çağlar Arisoy3Asli Ece Solmaz4Asli Gecgel5Haydar Çağatay Yüksel6Gökhan Şahin7Oguzcan Ozkan8Zeynep Sila Gokdere9Nilay Duman10Burçak Karaca11Division of Medical Oncology, Department of Internal Medicine, Ege University Medical Faculty, Izmir, TürkiyeDivision of Medical Oncology, Department of Internal Medicine, Ege University Medical Faculty, Izmir, TürkiyeDivision of Medical Oncology, Hatay Education and Research Hospital, Hatay, TürkiyeDepartment of Medical Genetics, Ege University Medical Faculty, Izmir, TürkiyeDepartment of Medical Genetics, Ege University Medical Faculty, Izmir, TürkiyeDivision of Medical Oncology, Department of Internal Medicine, Ege University Medical Faculty, Izmir, TürkiyeDivision of Medical Oncology, Department of Internal Medicine, Ege University Medical Faculty, Izmir, TürkiyeDivision of Medical Oncology, Department of Internal Medicine, Ege University Medical Faculty, Izmir, TürkiyeDivision of Medical Oncology, Department of Internal Medicine, Ege University Medical Faculty, Izmir, TürkiyeDivision of Medical Oncology, Department of Internal Medicine, Ege University Medical Faculty, Izmir, TürkiyeDepartment of Dermatology, Ege University Medical Faculty, Izmir, TürkiyeDivision of Medical Oncology, Department of Internal Medicine, Ege University Medical Faculty, Izmir, TürkiyeIntroductionImmune 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.MethodsIn 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.ResultsGenotyping 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:1.13–13.64; p=0.031). Subgroup analyses revealed a significant increase in risk across endocrine, non-cutaneous, multiple, low-grade, and early onset (<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: 1.14–12.61; p =0.030).DiscussionThese 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.https://www.frontiersin.org/articles/10.3389/fimmu.2025.1616325/fullimmune checkpoint inhibitorsrs16906115 polymorphismlymphocyte stability indexmelanomagenetic predispositionimmune-related adverse events |
| spellingShingle | Fatma Pınar Açar Caner Acar Damla Gunenc Çağlar Arisoy Asli Ece Solmaz Asli Gecgel Haydar Çağatay Yüksel Gökhan Şahin Oguzcan Ozkan Zeynep Sila Gokdere Nilay Duman Burçak Karaca Predicting immune-related adverse events in patients with melanoma: the role of interleukin-7 rs16906115 polymorphism and lymphocyte dynamics Frontiers in Immunology immune checkpoint inhibitors rs16906115 polymorphism lymphocyte stability index melanoma genetic predisposition immune-related adverse events |
| title | Predicting immune-related adverse events in patients with melanoma: the role of interleukin-7 rs16906115 polymorphism and lymphocyte dynamics |
| title_full | Predicting immune-related adverse events in patients with melanoma: the role of interleukin-7 rs16906115 polymorphism and lymphocyte dynamics |
| title_fullStr | Predicting immune-related adverse events in patients with melanoma: the role of interleukin-7 rs16906115 polymorphism and lymphocyte dynamics |
| title_full_unstemmed | Predicting immune-related adverse events in patients with melanoma: the role of interleukin-7 rs16906115 polymorphism and lymphocyte dynamics |
| title_short | Predicting immune-related adverse events in patients with melanoma: the role of interleukin-7 rs16906115 polymorphism and lymphocyte dynamics |
| title_sort | predicting immune related adverse events in patients with melanoma the role of interleukin 7 rs16906115 polymorphism and lymphocyte dynamics |
| topic | immune checkpoint inhibitors rs16906115 polymorphism lymphocyte stability index melanoma genetic predisposition immune-related adverse events |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2025.1616325/full |
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