Turning-off the YAP1 switches pro-tumorigenic cancer-associated fibroblasts to anti-tumor phenotype in prostate cancer

Prostate cancer (PCa) rarely responds to immune-checkpoint blockade (ICB) therapies. Cancer-associated fibroblasts (CAFs) are critical components of the immunologically cold tumor microenvironment and are considered a promising target to enhance the immunotherapy response. The aim of this study was to reveal the mechanisms and use the plasticity of CAFs to switch from pro-tumorigenic to anti-tumor phenotypes and enhance ICB in PCa. Here, we investigated the functions of ECM-CAF and Lym-CAF by fluorescence-activated cell sorting. We first applied a selection to exclude epithelial (EPCAM+), hematopoietic (CD45+) and endothelial (CD31+) cells, we next used ECM-CAF marker (CD248) or Lym-CAF marker (TSG6) to sort primary CAFs and performed RNA-seq. To investigate the changes of CAFs co-cultured with CD3+ T cells, we collected primary CAFs after co-cultured with CD3+ T cells for 48 h and performed RNA-seq.