Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Huanhuxi Road, Hexi District, Tianjin, 300060, China.
Key Laboratory of Cancer Prevention and Therapy, Huanhuxi Road, Hexi District, Tianjin, 300060, China.
J Leukoc Biol. 2024 Sep 2;116(3):579-588. doi: 10.1093/jleuko/qiae065.
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.
三阴性乳腺癌是一种高风险的乳腺癌形式，具有高转移潜能和缺乏有效治疗方法。免疫疗法已经显示出令人鼓舞的临床益处，其在三阴性乳腺癌中的疗效受肿瘤微环境中免疫细胞浸润的影响。PGAM1 是参与癌症代谢的关键酶；然而，其在肿瘤微环境中的作用尚不清楚。在这项研究中，我们旨在研究 PGAM1 在三阴性乳腺癌中的作用，并确定 PGAM1 抑制与抗 PD-1 免疫疗法联合的潜力。我们的结果表明，PGAM1 在三阴性乳腺癌中高度表达，与预后不良相关。体内实验表明，PGAM1 抑制与抗 PD-1 免疫疗法协同作用，显著重塑肿瘤微环境，导致抗肿瘤免疫细胞（如 CD8+T 细胞和 M1 巨噬细胞）增加，同时抑制性免疫细胞浸润减少，包括髓系来源的抑制细胞、M2 巨噬细胞和调节性 T 细胞。功能和动物实验表明，这种协同机制抑制了体外和体内的肿瘤生长。我们确定 PGAM1 是一种通过调节免疫细胞浸润发挥抗肿瘤作用的新型靶标。我们的结果表明，PGAM1 可以与抗 PD-1 免疫疗法协同作用，为三阴性乳腺癌提供一种新的治疗策略。
