Association between HLA-DRB1*04:05 and the efficacy of immune checkpoint inhibitors for patients with advanced cancer

Q: What did the results show regarding progression-free survival?

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.

Sep 22, 2026

Upload by Jasmine

Tumor cells suppress antitumor immunity by using immune checkpoint proteins such as programmed cell death 1, leading to widespread use of immune checkpoint inhibitors (ICIs) across malignancies. ICI-induced diabetes is rare yet life-threatening, and previous work linked baseline pancreatic beta-cell function to treatment outcomes. This study evaluates whether HLA class II alleles influence prognosis in advanced cancer patients receiving ICIs.

LanguageEnglish

CategoryResearch & Report

FormatPDF

Pages8

Reading Time20 min

AccessFree to download

Introduction

Methods

Results

Conclusions

TYPE Original Research PUBLISHED 10 June 2026 DOI 10.3389/fendo.2026.1789039 OPEN ACCESS EDITED BY Mutlu Demiray, Medicana Health Group, Türkiye REVIEWED BY Giandomenico Roviello, University of Firenze, Italy Tianchi Lu, City University of Hong Kong, Hong Kong SAR, China Hilada Neﬁc, University of Sarajevo, Bosnia and Herzegovina *CORRESPONDENCE Mayu Watanabe [mayuw294@gmail.com](mayuw294@gmail.com) RECEIVED 16 January 2026 REVISED 25 April 2026 ACCEPTED 19 May 2026 PUBLISHED 10 June 2026 CITATION Watanabe 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. Front. Endocrinol. 17:1789039 . doi: 10.3389/fendo.2026.1789039 COPYRIGHT © 2026 Watanabe, Eguchi, Takamoto and Wada. This is an open-access article distributed under the terms of the Creative 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. Association between HLADRB1*04:05 and the efﬁcacy of immune checkpoint inhibitors for patients with advanced cancer Mayu Watanabe 1,2*, Jun Eguchi 2, Atsushi Takamoto 3 and Jun Wada 2 1 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 Introduction: 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. Methods: 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. Conclusions: 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. KEYWORDS anti-PD1 immune checkpoint inhibitors, human leukocyte antigen class II alleles, progression-free survival, treatment response, type 1 diabetes Frontiers in Endocrinology 01 [frontiersin.org](frontiersin.org) 1 Introduction Tumor cells inhibit immune responses through immune checkpoint proteins such as programmed cell death 1 (PD-1) to escape immunological defenses. Immune checkpoint inhibitors (IC

FAQs

What was the main research question of this study?

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.

How many patients were included and how were HLA genotypes handled?

Ninety-six patients with advanced cancer were included, and HLA genotypes were evaluated to determine their association with cancer prognosis under ICI treatment.

What did the results show regarding progression-free survival?

Patients positive for DRB104:05 had a significantly shorter median progression-free survival than DRB104:05-negative patients, and multivariable Cox analysis showed DRB1*04:05 was independently associated with shorter PFS.

Sep 22, 2026

Upload by Jasmine