Tumour-infiltrating CD8+ T cells are often located within stromal-rich areas in the tumour and thus are in close contact with cancer-associated fibroblasts (CAFs). New research by Lakins et al. shows that CAFs are able to inhibit tumour-antigen-specific T cell activity through engaging in antigen processing and immune checkpoint ligand expression. CAFs isolated from murine lung tumours processed and cross-presented peptides of tumour cell-specific ovalbumin (OVA). In co-culture, tumour cell survival was significantly increased when T cells were pre-conditioned with OVA-presenting CAFs, owing to a reduction in T cell viability. This effect was dependent on increased programmed cell death 1 ligand 2 (PDL2) and FAS ligand expression on CAFs compared with normal fibroblasts, the inhibition of which led to reduced tumour growth in a mouse model.
Lakins, M. A. et al. Cancer-associated fibroblasts induce antigen-specific deletion of CD8+ T Cells to protect tumour cells. Nat. Commun. 9, 948 (2018)