A pan-cancer single-cell transcriptional analysis of antigen-presenting cancer-associated fibroblasts in the tumor microenvironment

Cancer-associated fibroblasts (CAFs) are the primary stromal cells found in tumor microenvironment, and display high plasticity and heterogeneity. By using single-cell RNA-seq technology, researchers have identified various subpopulations of CAFs, particularly highlighting a recently identified subpopulation termed antigen-presenting CAFs (apCAFs), which are largely unknown. We collected datasets from public databases for 9 different solid tumor types to analyze the role of apCAFs in the tumor microenvironment. Our data revealed that apCAFs, likely originating mainly from normal fibroblast, are commonly found in different solid tumor types and generally are associated with anti-tumor effects. apCAFs may be associated with the activation of CD4+ effector T cells and potentially promote the survival of CD4+ effector T cells through the expression of C1Q molecules. Moreover, apCAFs exhibited highly enrichment of transcription factors RUNX3 and IKZF1, along with increased glycolytic metabolism. Taken together, these findings offer novel insights into a deeper understanding of apCAFs and the potential therapeutic implications for apCAFs targeted immunotherapy in cancer.