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Demiray,  \nMedicana Health Group, Türkiye  \nREVIEWED BY  \nGiandomenico Roviello, University of Firenze, Italy Tianchi Lu,  \nCity University of Hong Kong, Hong Kong SAR, China  \nHilada Nefic,  \nUniversity of Sarajevo, Bosnia and Herzegovina  \n*CORRESPONDENCE  \nMayu Watanabe  \n [mayuw294@gmail.com](mayuw294@gmail.com)  \nRECEIVED 16 January 2026  \nREVISED 25 April 2026  \nACCEPTED 19 May 2026  \nPUBLISHED 10 June 2026  \nCITATION  \nWatanabe M, Eguchi J, Takamoto A and Wada J (2026) Association between HLA-DRB1*04:05 and the efficacy of immune checkpoint inhibitors for patients with advanced cancer.  \nFront. Endocrinol. 17:1789039 .  \ndoi: 10.3389/fendo.2026.1789039  \nCOPYRIGHT  \n© 2026 Watanabe, Eguchi, Takamoto and Wada. This is an open-access article distributed under the terms of the  \nCreative Commons Attribution License (CC BY) . The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.  \nAssociation between HLADRB1*04:05 and the efficacy of immune checkpoint inhibitors for patients with advanced cancer  \nMayu Watanabe 1,2*, Jun Eguchi 2, Atsushi Takamoto 3 and Jun Wada 2  \n1 Department of Diabetology and Endocrinology, NHO Okayama Medical Center, Okayama, Japan, 2 Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan, 3 Department of Urology, Fukuyama City Hospital, Hiroshima, Japan  \nIntroduction: Tumor cells use immune checkpoint proteins such as programmed cell death 1 to escape immunological defenses. Immune checkpoint inhibitors (ICIs) that target these proteins have been used to treat several malignancies. ICIinduced diabetes is a rare but life-threatening adverse event. Our previous study evaluated pancreatic b-cell activity using the homeostasis model assessment of b-cell (HOMA-b) function before ICI treatment and demonstrated its association with treatment outcomes. In addition, DRB1*04:05 and DRB1*09:01 reportedly increase the risk of type 1 diabetes in Japanese patients, whereas DRB1*15:01 protected against type 1 diabetes. However, the association between human leukocyte antigen (HLA) class II alleles and treatment outcomes of ICI therapy remains unclear.  \nMethods: We included 96 patients who were diagnosed with advanced cancer. The HLA genotypes that cause type 1 diabetes in patients with ICI-treated cancers were evaluated to determine their association with the cancer prognosis. Results: The median progression-free survival (PFS) in the DRB1*04:05-positive group (2 months, 95% confidence interval [CI]: 1.214–2.786; 31 events; 1 censored event) was significantly shorter than that in the DRB1*04:05-negative group (3 months; 95% CI: 1 .933–4. 067; 56 events; 8 censored events) (log rank p=0 . 045) . Additionally, a multivariable Cox proportional hazards regression revealed that DRB1*04:05 was independently associated with shorter PFS for patients treated with ICIs.  \nConclusions: HLA class II alleles were associated with shorter PFS in patients treated with ICIs. In particular, DRB1*04:05 positivity was associated with worse survival outcomes, suggesting a potential immunogenetic contribution to treatment outcomes.  \nKEYWORDS  \nanti-PD1 immune checkpoint inhibitors, human leukocyte antigen class II alleles, progression-free survival, treatment response, type 1 diabetes  \nFrontiers in Endocrinology 01 [frontiersin.org](frontiersin.org)  \n1 Introduction  \nTumor cells inhibit immune responses through immune checkpoint proteins such as programmed cell death 1 (PD-1) to escape immunological defenses. Immune checkpoint inhibitors (IC","cbCaihUDmoj4sixB","https://ap.wps.com/l/cbCaihUDmoj4sixB","pdf",469896,"English","# Introduction\n# Methods\n# Results\n# Conclusions","[{\"question\":\"What was the main research question of this study?\",\"answer\":\"Whether specific HLA class II alleles, particularly HLA-DRB1*04:05, are associated with treatment outcomes in advanced cancer patients treated with immune checkpoint inhibitors.\"},{\"question\":\"How many patients were included and how were HLA genotypes handled?\",\"answer\":\"Ninety-six patients with advanced cancer were included, and HLA genotypes were evaluated to determine their association with cancer prognosis under ICI treatment.\"},{\"question\":\"What did the results show regarding progression-free survival?\",\"answer\":\"Patients positive for DRB1*04:05 had a significantly shorter median progression-free survival than DRB1*04:05-negative patients, and multivariable Cox analysis showed DRB1*04:05 was independently associated with shorter PFS.\"}]","Association between HLA-DRB1*04:05 and the efficacy of immune checkpoint inhibitors for patients with advanced cancer | PDF",1790110193]