Retinoic Acid Reprograms Mast Cells Toward a Proinflammatory State to Enhance Antitumor Immunity
Source abstract
Abstract
Abstract Mast cells play complex and context‐dependent roles within the tumor microenvironment, yet their molecular characteristics and functional diversity across human cancers remain poorly defined. In this study, single‐cell RNA sequencing and spatial transcriptomics data are integrated to comprehensively map the transcriptional and spatial heterogeneity of mast cells across ten cancer types. A distinct proinflammatory mast cell (PMC) population is identified, characterized by strong antigen‐presenting features and immune‐activating potential. Mechanistic analyses show that retinoic acid (RA) signaling drives the polarization of PMCs through activation of RARα, which promotes CIITA‐mediated MHC‐II expression, CXCL16 secretion, and T cell recruitment and activation. Across multiple cancer types, tumors with higher PMC abundance are associated with more favorable clinical outcomes. These findings reveal the pivotal role of RA–RARα–CIITA signaling in mast cell reprogramming and suggest that pharmacologic induction of proinflammatory mast cells may represent a promising approach to enhance antitumor immunity.
Source: crossref · Quality: baseline
Research context
OpenAlex topics: Mast cells and histamine · Retinoids in leukemia and cellular processes · Single-cell and spatial transcriptomics
SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.
Affiliations
Department of Oral and Maxillofacial Surgery Sun Yat‐sen Memorial Hospital of Sun Yat‐sen University Guangzhou 510120 China
Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation Guangdong‐Hong Kong Joint Laboratory for RNA Medicine Medical Research Center Sun Yat‐sen Memorial Hospital Sun Yat‐sen University Guangzhou 510120 China
Department of Pathology Sun Yat‐sen Memorial Hospital Sun Yat‐sen University Guangzhou 510120 China
Department of Stomatology Affiliated Hospital of Hangzhou Normal University Hangzhou 310015 China
Department of Stomatology Shunde Hospital Southern Medical University (The First People's Hospital of Shunde) Foshan 528308 China
Guanghua School of Stomatology Hospital of Stomatology Guangdong Province Key Laboratory of Stomatology Sun Yat‐sen University Guangzhou 510095 China
Medical Research Center Sun Yat‐sen Memorial Hospital Sun Yat‐sen University Guangzhou 510120 China
School of Mathematics and Big Data Foshan University Southern Medical University Foshan 528000 Guangzhou 510000 China
Department of Endodontics Stomatological Hospital Southern Medical University Guangzhou 510000 China
Funding
National Natural Science Foundation of China · Basic and Applied Basic Research Foundation of Guangdong Province · China Postdoctoral Science Foundation
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