CD160 expression on CD8+ T cells is associated with active effector responses but limited activation potential in pancreatic cancer

CD160 is an Ig-like glycoprotein expressed by the majority of circulating natural killer cells and gamma delta T cells. Whether CD160 could regulate CD8(+) T-cell functions remains unknown. In this study, we investigated the effects of CD160 on CD8(+) T cells in pancreatic cancer. First, we found that the frequency of PD-1(+) cells was comparable between CD160(+) and CD160(-)CD8(+) T cells, with the former presenting significantly higher PD-1 expression level. In contrast, the frequency of TIM-3(+) cells was higher among CD160(+) cells but the expression level was comparable between CD160(+) and CD160(-)CD8(+) T cells. The IFN-gamma and IL-2-expressing CD8(+) T cells, directly ex vivo, were highly enriched in the CD160(+) subset. However, when CD160(+) and CD160(-)CD8(+) T cells were stimulated, the proliferation levels of CD160(+) and CD160(-) cells were initially comparable, but were significantly lower in CD160(+)CD8(+) T cells than in CD160(-)CD8(+) T cells later on. The IFN-gamma and IL-2 transcription levels were initially higher in CD160(+)CD8(+) T cells, but eventually reduced in CD160(+)CD8(+) T cells compared to CD160(-)CD8(+) T cells. Also, CD160(+)CD8(+) T cells presented lower cytotoxic capacity than CD160(-)CD8(+) T cells. Interestingly, we observed that tumor-infiltrating CD8(+) T cells were significantly enriched with the CD160(+) subset in pancreatic cancer patients. In addition, patients with higher frequencies of tumor CD160(+)CD8(+) T cells presented lower survival. Overall, these data demonstrated that tumor-infiltrating CD8(+) T cells were enriched with the CD160(+) subset in pancreatic cancer, with active effector responses directly ex vivo but limited potential for further activation.