文章：

磷酸甘油酸变位酶1通过诱导免疫抑制性M2型巨噬细胞促进乳腺癌进展

Phosphoglycerate mutase 1 promotes breast cancer progression through inducing immunosuppressive M2 macrophages 

原文发布日期：2024-05-15 

英文摘要：

Immunosuppressive tumor microenvironment (TME) contributes to tumor progression and causes major obstacles for cancer therapy. Phosphoglycerate mutase 1 (PGAM1) is a key enzyme involved in cancer metabolism while its role in remodeling TME remains unclear. In this study, we reported that PGAM1 suppression in breast cancer (BC) cells led to a decrease in M2 polarization, migration, and interleukin-10 (IL-10) production of macrophages. PGAM1 regulation on CCL2 expression was essential to macrophage recruitment, which further mediated by activating JAK-STAT pathway. Additionally, the CCL2/CCR2 axis was observed to participate in PGAM1-mediated immunosuppression via regulating PD-1 expression in macrophages. Combined targeting of PGAM1 and the CCL2/CCR2 axis led to a reduction in tumor growth in vivo. Furthermore, clinical validation in BC tissues indicated a positive correlation between PGAM1, CCL2 and macrophage infiltration. Our study provides novel insights into the induction of immunosuppressive TME by PGAM1 and propose a new strategy for combination therapies targeting PGAM1 and macrophages in BC. 

摘要翻译：

免疫抑制性肿瘤微环境（TME）促进肿瘤进展并成为癌症治疗的主要障碍。磷酸甘油酸变位酶1（PGAM1）是癌症代谢中的关键酶，但其在重塑TME中的作用尚不明确。本研究发现，抑制乳腺癌（BC）细胞中的PGAM1可降低巨噬细胞的M2极化、迁移能力和白细胞介素-10（IL-10）产生。PGAM1通过激活JAK-STAT通路调控CCL2表达，这对巨噬细胞招募至关重要。此外，CCL2/CCR2轴通过调节巨噬细胞中PD-1表达参与PGAM1介导的免疫抑制。联合靶向PGAM1与CCL2/CCR2轴可抑制体内肿瘤生长。临床组织学验证显示BC组织中PGAM1、CCL2与巨噬细胞浸润呈正相关。本研究为PGAM1诱导免疫抑制性TME提供了新机制，并为乳腺癌中联合靶向PGAM1与巨噬细胞的治疗策略提供了理论依据。

原文链接：

Phosphoglycerate mutase 1 promotes breast cancer progression through inducing immunosuppressive M2 macrophages