The common lack of response to immunotherapy in solid tumours can be explained by a number of factors, including irreversible CD8+ T-cell dysfunction, scarcity of antigens and/or mutations in the antigen-presentation machinery.64 CD8+ cells can also be excluded from, or trapped within, tumours by the dense, fibrotic extracellular matrix produced by cancer-associated fibroblasts (CAFs). This evidence concerns the gene CD8A and cancer.