Intraepithelial Cd94+Tumor-Infiltrating Lymphocytes In A Context Of Hla-E Overexpression As A New Immune Checkpoint To Predict Prognosis In Colorectal Carcinomas.

e14592Background: A better understanding of the immune-modulating interactions between tumor cells and immune cells underlying the balance between immune control and immune resistance in colorectal cancer (CRC) is crucial for the design of immunotherapies. We have previously demonstrated that overexpression of the human MHC class Ib molecule - HLA-E/β2 microglobulin - by tumor cells in CRC was associated with an unfavorable prognosis, suggesting its involvement in immune escape. However, the specific receptor of HLA-E/β2m - CD94/NKG2A, inhibitory or CD94/NKG2C, activating - expressed by tumor-infiltrating lymphocytes (TIL), as well as the influence of the microsatellite status in HLA-E/β2m overexpression, remain unknown. Methods: We investigated in the primary tumor of 245 CRC patients 1) the association of HLA-E/β2m overexpression and the density of CD94+ intraepithelial TIL (IEL-TIL) with the microsatellite status, 2) the nature of CD94+ TIL and the receptor expressed - CD94/NKG2A or CD94/NKG2C - and 3)...