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

The presence of precursor to exhausted (T-pex) 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 (Tcf7) by CD8(+) T cells predicted improved patient prognosis and T(pex )cells (CD3(+)CD8(+)TCF-1(+)PD-1(+)) were abundant within lymphoid aggregates of stage III CRCs. In contrast, CD3(+)CD8(+)TCF-1(-)PD-1(+ )cells were more abundant at the invasive front and tumor core, while gamma delta T cells were equally abundant in all tumor areas. Interestingly, no differences in the frequency of T-pex cells were observed between TIL-hi dMMR and TIL-hi pMMR CRCs. Therefore, T-pex cell function and ICI response rates in TIL-hi CRC warrants further investigation.