T cell factor 1 (TCF-1) defines T cell differentiation in colorectal cancer.

The presence of precursor to exhausted (T) CD8 T cells is important to maintain robust immunity following treatment with immune checkpoint inhibition (ICI). Impressive responses to ICI are emerging in patients with stage II-III mismatch repair (MMR)-deficient (dMMR) colorectal cancer (CRC). We found 64% of dMMR and 15% of mismatch repair-proficient (pMMR) stage III CRCs had a high frequency of tumor infiltrating lymphocytes (TIL-hi). Furthermore, expression of TCF-1 by CD8 T cells predicted improved patient prognosis and T cells (CD3CD8TCF-1PD-1) were abundant within lymphoid aggregates of stage III CRCs. In contrast, CD3CD8TCF-1PD-1 cells were more abundant at the invasive front and tumor core, while γδ T cells were equally abundant in all tumor areas. Interestingly, no differences in the frequency of T cells were observed between TIL-hi dMMR and TIL-hi pMMR CRCs. Therefore, T cell function and ICI response rates in TIL-hi CRC warrants further investigation.