Analyzing scRNAseq data from 38 patients with gastric cancer (GC), Song, Wei, Liu, et al. identified antigen-presenting CAF (apCAF) with high MHC-II expression that spatially localized near tertiary lymphoid structures in the TME. The high apCAF group was associated with a favorable prognosis and a significantly longer survival time in GC. ApCAFs promoted T cell activation and proliferation, enhanced T cell cytotoxicity, and supported proinflammatory macrophage polarization, which then, in a positive feedback loop, increased apCAF generation. Baseline tumors in immunotherapy responders from a variety of cancer types exhibited higher apCAF levels.
Contributed by Katherine Turner
ABSTRACT: Cancer-associated fibroblasts (CAF) play a crucial role in tumor progression and immune regulation. However, the functional heterogeneity of CAFs remains unclear. Here, we identify antigen-presenting CAFs (apCAF), characterized by high MHC II expression, in gastric cancer (GC) tumors and find that apCAFs are preferentially located near tertiary lymphoid structures. Both in vivo and in vitro experiments demonstrate that apCAFs promote T cell activation and enhances its cytotoxic and proliferative capacities, thereby strengthening T cell-mediated anti-tumor immunity. Additionally, apCAFs facilitate the polarization of macrophages toward a pro-inflammatory phenotype. These polarized macrophages, in turn, promote the formation of apCAFs, creating a positive feedback loop that amplifies anti-tumor immune responses. Notably, baseline tumors in immunotherapy responders across various cancer types exhibit higher levels of apCAFs infiltration. This study advances the understanding of CAFs heterogeneity in GC and highlights apCAFs as a potential biomarker for predicting immunotherapy response in pan-cancer.
Author Info: (1) Department of Gastric Surgery, Fudan University Shanghai Cancer Center, Shanghai, China. Department of Oncology, Shanghai Medical College of Fudan University, Shanghai, China.
Author Info: (1) Department of Gastric Surgery, Fudan University Shanghai Cancer Center, Shanghai, China. Department of Oncology, Shanghai Medical College of Fudan University, Shanghai, China. (2) Department of Gastric Surgery, Fudan University Shanghai Cancer Center, Shanghai, China. Department of Oncology, Shanghai Medical College of Fudan University, Shanghai, China. (3) Department of Gastric Surgery, Fudan University Shanghai Cancer Center, Shanghai, China. Department of Oncology, Shanghai Medical College of Fudan University, Shanghai, China. (4) Department of Gastric Surgery, Fudan University Shanghai Cancer Center, Shanghai, China. Department of Oncology, Shanghai Medical College of Fudan University, Shanghai, China. (5) Department of Gastric Surgery, Fudan University Shanghai Cancer Center, Shanghai, China. Department of Oncology, Shanghai Medical College of Fudan University, Shanghai, China. (6) Department of Gastric Surgery, Fudan University Shanghai Cancer Center, Shanghai, China. drwangyn@126.com. Department of Oncology, Shanghai Medical College of Fudan University, Shanghai, China. drwangyn@126.com. (7) Department of Gastric Surgery, Fudan University Shanghai Cancer Center, Shanghai, China. fenglinliu@hotmail.com. Department of Oncology, Shanghai Medical College of Fudan University, Shanghai, China. fenglinliu@hotmail.com. (8) Department of Gastric Surgery, Fudan University Shanghai Cancer Center, Shanghai, China. liuxw1129@hotmail.com. Department of Oncology, Shanghai Medical College of Fudan University, Shanghai, China. liuxw1129@hotmail.com.
