1. PGAM1 suppression remodels the tumor microenvironment in triple-negative breast cancer and synergizes with anti-PD-1 immunotherapy.
- Author
-
Zhang D, Wang M, Wang W, Ma S, Yu W, Ren X, and Sun Q
- Subjects
- Humans, Female, Animals, Mice, Cell Line, Tumor, Immune Checkpoint Inhibitors pharmacology, Immune Checkpoint Inhibitors therapeutic use, Programmed Cell Death 1 Receptor antagonists & inhibitors, Mice, Inbred BALB C, Triple Negative Breast Neoplasms immunology, Triple Negative Breast Neoplasms pathology, Triple Negative Breast Neoplasms therapy, Triple Negative Breast Neoplasms drug therapy, Tumor Microenvironment drug effects, Tumor Microenvironment immunology, Immunotherapy methods
- Abstract
Triple-negative breast cancer is a high-risk form of breast cancer with a high metastatic potential and lack of effective therapies. Immunotherapy has shown encouraging clinical benefits, and its efficacy in triple-negative breast cancer is affected by immunocyte infiltration in the tumor microenvironment. PGAM1 is a key enzyme involved in cancer metabolism; however, its role in the tumor microenvironment remains unclear. In this study, we aimed to investigate the role of PGAM1 in triple-negative breast cancer and determine the potential of PGAM1 inhibition in combination with anti-PD-1 immunotherapy. Our results showed that PGAM1 is highly expressed in triple-negative breast cancer and is associated with poor prognosis. In vivo experiments demonstrated that PGAM1 inhibition synergizes with anti-PD-1 immunotherapy, significantly remodeling the tumor microenvironment and leading to an increase in antitumor immunocytes, such as CD8+ T cells and M1 macrophages, and a reduction in immunosuppressive cell infiltration, including myeloid-derived suppressor cells, M2 macrophages, and regulatory T cells. Functional and animal experiments showed that this synergistic mechanism inhibited tumor growth in vitro and in vivo. We identified PGAM1 as a novel target that exhibits an antitumor effect via the regulation of immunocyte infiltration. Our results show that PGAM1 can synergize with anti-PD-1 immunotherapy, providing a novel treatment strategy for triple-negative breast cancer., Competing Interests: Conflict of interest statement. All the authors declare no potential competing interests., (© The Author(s) 2024. Published by Oxford University Press on behalf of Society for Leukocyte Biology. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)
- Published
- 2024
- Full Text
- View/download PDF