CRC-derived cross-presenting cancer-associated fibroblasts cognately interact with CD8+ T cells to suppress T cell activation, decrease cytotoxicity, and increase exhaustion marker expression, which is associated with upregulated lysosomal protease cathepsin S expression and boosted capacity to cross-present neoantigen-derived synthetic long peptides of cancer-associated fibroblasts (144). The gene discussed is CTSS; the disease is cancer.