,41 Although on the basis of our in vitro functional polyclonal assay we cannot distinguish between any direct or indirect effects on CD4+ (FoxP3+) or CD8+ TIL, these findings by us and others suggest that immunotherapeutic targeting of GITR may stimulate the local immune response within the CRC-/CRLM-related TME through affecting both Treg and aTh cell function. This evidence concerns the gene TNFRSF18 and colorectal carcinoma.