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 γδ 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-γ 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-γ 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.