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ORIGINAL RESEARCH article
Front. Immunol.
Sec. Cancer Immunity and Immunotherapy
Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1472197
This article is part of the Research Topic The Innate Immune System as a Driver of Diabetes and its Complications View all articles
Association of Type 2 Diabetes, Hypertension, and Hyperlipidemia with Immune-Related Adverse Events in Patients Undergoing Immune Checkpoint Inhibitors Therapy
Provisionally accepted- 1 West China School of Medicine, West China Hospital, Sichuan University, Chengdu, Sichuan Province, China
- 2 Hangzhou Linan Guorui Health Industry Investment Co.,Ltd,, Hangzhou, Jiangsu Province, China
Abstract Aims: Immune-related adverse events (irAEs) pose a significant challenge to the clinical use of immune checkpoint inhibitors (ICIs) in cancer immunotherapy. This study aims to determine whether comorbid conditions such as type 2 diabetes (T2DM), hypertension, and hyperlipidemia affect the risk of irAEs in cancer patients receiving ICIs treatments. Materials and methods: We conducted a retrospective analysis of clinical data from 3,489 cancer patients treated with ICIs (anti-PD-1, anti-PD-L1, and anti-CTLA-4) at West China Hospital of Sichuan University from 2017 to 2022. Logistic regression models were used to evaluate the associations between T2DM, hypertension, and hyperlipidemia with irAEs. Subgroup analyses assessed irAEs in patients with and without these comorbidities across different cancer types. Additionally, we explored the associations between comorbidities and irAEs affecting different organs. Results: The results showed that comorbid T2DM, hypertension, and hyperlipidemia significantly increased the risk of irAEs in all cancer types (T2DM: OR=1.40, 95% CI: 1.12-1.74, p=0.003; hypertension: OR=1.21, 95% CI: 1.00-1.45, p=0.049; hyperlipidemia: OR=1.62, 95% CI: 1.02-2.53, p=0.038). T2DM primarily increased the risk of irAEs in lung cancer patients (OR = 1.50, 95% CI: 1.12-2.01, FDR-adjusted p = 0.036), and all three comorbidities significantly elevated the risk of cardiac irAEs. Conclusions: Our study is the first to confirm an association between T2DM, hypertension, and hyperlipidemia and the occurrence of irAEs in cancer patients receiving ICIs therapy. This finding highlights the critical need for clinicians to perform comprehensive evaluations of patients' comorbidities prior to treatment.
Keywords: immune checkpoint inhibitors, Immune-related adverse events, type 2 diabetes, Hypertension, Hyperlipidemia
Received: 29 Jul 2024; Accepted: 20 Feb 2025.
Copyright: © 2025 Li, Mu, Liu, Huang and Peng. 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) or licensor 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.
* Correspondence:
Xingchen Peng, West China School of Medicine, West China Hospital, Sichuan University, Chengdu, 610000, Sichuan Province, China
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