---
title: "Immune checkpoints in metabolic diseases and cancer: mechanisms and therapeutic potential"
id: "pubmed-42680727"
canonical_url: "https://medichelpline.com/clinical-feed/pubmed-42680727"
content_type: "clinical_feed_article"
specialty: "Pharmacology"
source_name: "PubMed / NCBI"
source_url: "https://pubmed.ncbi.nlm.nih.gov/42680727/"
doi: "10.1038/s41392-026-02810-5"
published_at: "2026-09-02T00:00:00.000Z"
evidence_level: "Journal Article"
license: "CC-BY-NC-4.0 / Informational Use"
---
# Immune checkpoints in metabolic diseases and cancer: mechanisms and therapeutic potential
## Provenance & Clinical Metadata
- **Canonical URL:** https://medichelpline.com/clinical-feed/pubmed-42680727
- **Specialty:** [Pharmacology](https://medichelpline.com/clinical-feed/pharmacology.md)
- **Primary Source:** PubMed / NCBI
- **Source URL:** [Original Journal Publication](https://pubmed.ncbi.nlm.nih.gov/42680727/)
- **DOI:** [10.1038/s41392-026-02810-5](https://doi.org/10.1038%2Fs41392-026-02810-5)
- **Published At:** 2026-09-02T00:00:00.000Z
- **Evidence Rating:** Journal Article
## Executive GIST (TL;DR)
- The global burden of **metabolic diseases**—notably **obesity**, **diabetes mellitus**, and **thyroid disorders**—has increased markedly, and current pharmacologic treatments have limitations including adverse effects and resistance. - **Immune checkpoint** molecules, first characterized for their role in cancer immunotherapy, also influence metabolic homeostasis through modulation of inflammation and energy metabolism. - The **PD-1/PD-L1** axis is highlighted as a central pathway that exerts dual roles in immune regulation and metabolic modulation by shaping inflammatory responses and cellular metabolism. - In obesity, PD-1/PD-L1 signaling can promote macrophage polarization from proinflammatory M1 toward anti-inflammatory M2 phenotypes within adipose tissue, reducing chronic low-grade inflammation and related metabolic dysfunction. - Evidence suggests immune checkpoint pathways have potential as novel therapeutic targets for metabolic disorders, but this area remains underexplored compared with oncology. - The review synthesizes pathophysiological mechanisms linking immune checkpoints to **obesity**, **diabetes**, and **thyroid disease**, and discusses translational opportunities and possible directions for clinical intervention. - The authors emphasize the need for more comprehensive research and clinical studies to clarify mechanisms, safety, and efficacy of immune checkpoint modulation in metabolic disease contexts. - The article is a narrative review summarizing mechanistic insights and proposing future translational priorities; specific trial data or quantitative outcomes were not reported in the source abstract. - The authors declare no competing interests; one author is on the journal editorial board but was not involved in handling the manuscript. - The review aims to bridge knowledge from cancer immunotherapy into metabolic disease therapeutics, proposing immune checkpoint modulation as an alternative or adjunct to conventional pharmacotherapy.
## Clinical Analysis & Structured Key Points
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Affiliations Expand ### Affiliations * 1 Department of Pathology, Xiangya Hospital, Central South University, Changsha, China. * 2 Department of Oncology, Institute of Medical Sciences, National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China. shuangliu2016@csu.edu.cn. * 3 Department of Pathology, Xiangya Hospital, Central South University, Changsha, China. xdsh96@csu.edu.cn. * 4 Department of Pathology, Xiangya School of Basic Medicine, Central South University, Changsha, China. xdsh96@csu.edu.cn. * 5 Department of Pathology, Xiangya Hospital, Central South University, Changsha, China. taoyong@csu.edu.cn. * 6 NHC Key Laboratory of Carcinogenesis (Central South University), Key Laboratory of Carcinogenesis and Cancer Invasion (Ministry of Education), Cancer Research Institute and School of Basic Medicine, Central South University, Changsha, China. taoyong@csu.edu.cn. * PMID: **42680727** * DOI: [ 10.1038/s41392-026-02810-5 ](https://doi.org/10.1038/s41392-026-02810-5) Item in Clipboard Review # Immune checkpoints and immunoregulation in metabolic diseases and cancers: pathological mechanisms and therapeutic potential Minmin Xiang et al. Signal Transduct Target Ther. 2026. Show details Display options Display options Format Abstract PubMed PMID Signal Transduct Target Ther Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Signal+Transduct+Target+Ther%22%5Bjour%5D&sort=date&sort_order=desc) * [ Search in NLM Catalog ](https://www.ncbi.nlm.nih.gov/nlmcatalog?term=%22Signal+Transduct+Target+Ther%22%5BTitle+Abbreviation%5D) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42680727/) . 2026 Sep 2;11(1):360. doi: 10.1038/s41392-026-02810-5. ### Authors [Minmin Xiang](https://pubmed.ncbi.nlm.nih.gov/?term=Xiang+M&cauthor_id=42680727)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42680727/#short-view-affiliation-1 "Department of Pathology, Xiangya Hospital, Central South University, Changsha, China."), [Shuang Liu](https://pubmed.ncbi.nlm.nih.gov/?term=Liu+S&cauthor_id=42680727)[ 2 ](https://pubmed.ncbi.nlm.nih.gov/42680727/#short-view-affiliation-2 "Department of Oncology, Institute of Medical Sciences, National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China. shuangliu2016@csu.edu.cn."), [Desheng Xiao](https://pubmed.ncbi.nlm.nih.gov/?term=Xiao+D&cauthor_id=42680727)[ 3 ](https://pubmed.ncbi.nlm.nih.gov/42680727/#short-view-affiliation-3 "Department of Pathology, Xiangya Hospital, Central South University, Changsha, China. xdsh96@csu.edu.cn.")[ 4 ](https://pubmed.ncbi.nlm.nih.gov/42680727/#short-view-affiliation-4 "Department of Pathology, Xiangya School of Basic Medicine, Central South University, Changsha, China. xdsh96@csu.edu.cn."), [Yongguang Tao](https://pubmed.ncbi.nlm.nih.gov/?term=Tao+Y&cauthor_id=42680727)[ 5 ](https://pubmed.ncbi.nlm.nih.gov/42680727/#short-view-affiliation-5 "Department of Pathology, Xiangya Hospital, Central South University, Changsha, China. taoyong@csu.edu.cn.")[ 6 ](https://pubmed.ncbi.nlm.nih.gov/42680727/#short-view-affiliation-6 "NHC Key Laboratory of Carcinogenesis \(Central South University\), Key Laboratory of Carcinogenesis and Cancer Invasion \(Ministry of Education\), Cancer Research Institute and School of Basic Medicine, Central South University, Changsha, China. taoyong@csu.edu.cn.") ### Affiliations * 1 Department of Pathology, Xiangya Hospital, Central South University, Changsha, China. * 2 Department of Oncology, Institute of Medical Sciences, National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China. shuangliu2016@csu.edu.cn. * 3 Department of Pathology, Xiangya Hospital, Central South University, Changsha, China. xdsh96@csu.edu.cn. * 4 Department of Pathology, Xiangya School of Basic Medicine, Central South University, Changsha, China. xdsh96@csu.edu.cn. * 5 Department of Pathology, Xiangya Hospital, Central South University, Changsha, China. taoyong@csu.edu.cn. * 6 NHC Key Laboratory of Carcinogenesis (Central South University), Key Laboratory of Carcinogenesis and Cancer Invasion (Ministry of Education), Cancer Research Institute and School of Basic Medicine, Central South University, Changsha, China. taoyong@csu.edu.cn. * PMID: **42680727** * DOI: [ 10.1038/s41392-026-02810-5 ](https://doi.org/10.1038/s41392-026-02810-5) Item in Clipboard Cite Display options Display options Format Abstract PubMed PMID ## Abstract The global prevalence of metabolic diseases, notably obesity, diabetes mellitus, and thyroid disorders, has risen dramatically in recent decades, posing a significant threat to public health. While conventional pharmacological interventions remain the cornerstone of management, they face considerable limitations, including adverse effects and the development of drug resistance, underscoring the urgent need for alternative therapeutic strategies. Intriguingly, immune checkpoint molecules, originally recognized for their transformative role in cancer immunotherapy, are now gaining attention as pivotal regulators of metabolic homeostasis. Growing research demonstrates that immune checkpoint pathways, particularly the PD-1/PD-L1 axis, play dual roles in immune regulation and metabolic modulation by orchestrating inflammatory responses and energy metabolism. For instance, in obesity, PD-1/PD-L1 signaling promotes the polarization of adipose tissue macrophages from a proinflammatory M1 phenotype toward an anti-inflammatory M2 state, thereby mitigating chronic low-grade inflammation and associated metabolic dysfunction. These findings highlight the potential of immune checkpoint modulation as a novel therapeutic strategy for metabolic disorders. However, despite these advances, the role of immune checkpoints in metabolic diseases remains underexplored, with limited comprehensive reviews on the subject. This review comprehensively elucidates the pathophysiological mechanisms and translational potential of immune checkpoint regulation in obesity, diabetes, and thyroid disease while proposing novel directions for clinical intervention. © 2026. The Author(s). [PubMed Disclaimer](https://pubmed.ncbi.nlm.nih.gov/disclaimer/) ## Conflict of interest statement Competing interests: The authors declare no competing interests. Yongguang Tao is the editorial board member of Signal Transduction and Targeted Therapy, but he has not been involved in the process of manuscript handling. ## References 1. 1. He, X. & Xu, C. Immune checkpoint signaling and cancer immunotherapy. Cell Res. 30, 660–669 (2020). - [DOI](https://doi.org/10.1038/s41422-020-0343-4) - [PubMed](https://pubmed.ncbi.nlm.nih.gov/32467592/) 2. 1. Pardoll, D. M. The blockade of immune checkpoints in cancer immunotherapy. Nat. Rev. Cancer 12, 252–264 (2012). - [DOI](https://doi.org/10.1038/nrc3239) - [PubMed](https://pubmed.ncbi.nlm.nih.gov/22437870/) - [PMC](https://pmc.ncbi.nlm.nih.gov/articles/4856023/) 3. 1. Wu, T. & Dai, Y. Tumor microenvironment and therapeutic response. Cancer Lett. 387, 61–68 (2017). - [PubMed](https://pubmed.ncbi.nlm.nih.gov/26845449/) - [DOI](https://doi.org/10.1016/j.canlet.2016.01.043) 4. 1. Chow, A., Perica, K., Klebanoff, C. A. & Wolchok, J. D. Clinical implications of T cell exhaustion for cancer immunotherapy. Nat. Rev. Clin. Oncol. 19, 775–790 (2022). - [DOI](https://doi.org/10.1038/s41571-022-00689-z) - [PubMed](https://pubmed.ncbi.nlm.nih.gov/36216928/) - [PMC](https://pmc.ncbi.nlm.nih.gov/articles/10984554/) 5. 1. Morad, G., Helmink, B. A., Sharma, P. & Wargo, J. A. Hallmarks of response, resistance, and toxicity to immune checkpoint blockade. Cell 184, 5309–5337 (2021). - [PubMed](https://pubmed.ncbi.nlm.nih.gov/34624224/) - [PMC](https://pmc.ncbi.nlm.nih.gov/articles/8767569/) - [DOI](https://doi.org/10.1016/j.cell.2021.09.020) Show all 433 references ## Publication types * Review Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Review%22%5Bpt%5D&sort=date&sort_order=desc) * [ Search in MeSH ](https://www.ncbi.nlm.nih.gov/mesh?term=Review) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42680727/) ## MeSH terms * Animals Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Animals%22%5BMeSH%5D&sort=date&sort_order=desc) * [ Search in MeSH ](https://www.ncbi.nlm.nih.gov/mesh?term=Animals) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42680727/) * Humans Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Humans%22%5BMeSH%5D&sort=date&sort_order=desc) * [ Search in MeSH ](https://www.ncbi.nlm.nih.gov/mesh?term=Humans) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42680727/) * Immunotherapy Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Immunotherapy%22%5BMeSH%5D&sort=date&sort_order=desc) * [ Search in MeSH ](https://www.ncbi.nlm.nih.gov/mesh?term=Immunotherapy) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42680727/) * Macrophages / immunology Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Macrophages%2Fimmunology%22%5BMeSH%5D&sort=date&sort_order=desc) * [ Search in MeSH ](https://www.ncbi.nlm.nih.gov/mesh?term=Macrophages) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42680727/) * Metabolic Diseases* / genetics Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Metabolic+Diseases%2Fgenetics%22%5BMAJR%5D&sort=date&sort_order=desc) * [ Search in MeSH ](https://www.ncbi.nlm.nih.gov/mesh?term=Metabolic+Diseases) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42680727/) * Metabolic Diseases* / immunology Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Metabolic+Diseases%2Fimmunology%22%5BMAJR%5D&sort=date&sort_order=desc) * [ Search in MeSH ](https://www.ncbi.nlm.nih.gov/mesh?term=Metabolic+Diseases) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42680727/) * Metabolic Diseases* / pathology Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Metabolic+Diseases%2Fpathology%22%5BMAJR%5D&sort=date&sort_order=desc) * [ Search in MeSH ](https://www.ncbi.nlm.nih.gov/mesh?term=Metabolic+Diseases) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42680727/) * Metabolic Diseases* / therapy Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Metabolic+Diseases%2Ftherapy%22%5BMAJR%5D&sort=date&sort_order=desc) * [ Search in MeSH ](https://www.ncbi.nlm.nih.gov/mesh?term=Metabolic+Diseases) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42680727/) * Neoplasms* / genetics Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Neoplasms%2Fgenetics%22%5BMAJR%5D&sort=date&sort_order=desc) * [ Search in MeSH ](https://www.ncbi.nlm.nih.gov/mesh?term=Neoplasms) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42680727/) * Neoplasms* / immunology Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Neoplasms%2Fimmunology%22%5BMAJR%5D&sort=date&sort_order=desc) * [ Search in MeSH ](https://www.ncbi.nlm.nih.gov/mesh?term=Neoplasms) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42680727/) * Neoplasms* / pathology Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Neoplasms%2Fpathology%22%5BMAJR%5D&sort=date&sort_order=desc) * [ Search in MeSH ](https://www.ncbi.nlm.nih.gov/mesh?term=Neoplasms) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42680727/) * Neoplasms* / therapy Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Neoplasms%2Ftherapy%22%5BMAJR%5D&sort=date&sort_order=desc) * [ Search in MeSH ](h
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