Macrophage efferocytosis mediated by the TP63-RAC2 pathway promotes immunosuppressive remodeling in esophageal cancer
Year: 2025
Type: article
Abstract: This study explores the role of efferocytosis in esophageal squamous cell carcinoma (ESCC) using single-cell RNA sequencing and in vitro/in vivo assays. Analyzing 27 samples from 9 patients with ESCC, we identify diverse cell types and significant heterogeneity in the tumor microenvironment, with a focus on efferocytosis. Our findings highlight that macrophages engulf apoptotic tumor cells, thereby impairing immune responses and promoting tumor progression. Notably, TP63 and RAC2 emerge as key regulators of this process, influencing efferocytosis and immune modulation. Functional assays demonstrate that disrupting these pathways alters macrophage efferocytosis and impacts tumor growth in vivo. These results suggest that targeting efferocytosis pathways offers potential therapeutic strategies for ESCC, enhancing antitumor immunity and improving patient outcomes. The study underscores the complex interactions between tumor cells and the immune system, with efferocytosis representing a promising therapeutic target.
Source: Cell Reports Medicine
Authors: Yong Xi, Zhijie Zhao, Yundong Zhou, Chengliang Yin, Yuxin Li, Xiao Xu, Wenyi Jin, Chengbin Lin, Kui Zhao, Junjie Kuang, Senlian Hong, Bentong Yu, João Conde, Shiyuan Liu, Weiyu Shen
Institutions: Ningbo University, Ningbo Medical Center Lihuili Hospital, First Affiliated Hospital of Nanchang University, Shanghai Jiao Tong University, Shanghai Ninth People's Hospital, University of Malaya, Peking University, State Key Laboratory of Natural and Biomimetic Drugs, Fudan University, Zhongshan Hospital, City University of Hong Kong, Wuhan University, Renmin Hospital of Wuhan University, Yunnan University of Traditional Chinese Medicine, Guangxi Medical University, Comprehensive Health Research Centre, Universidade Nova de Lisboa, Second Affiliated Hospital of Xi'an Jiaotong University
Language: English
Subfield: Immunology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $5,620
OpenAlex ID: W4417534926