Fig. 78 (abstract P382).

In vitro NK cell exhaustion. CEACAM-1 was recently discovered as a necessary co-receptor and ligand of Tim-3 on T cells [4] functioning both in cis and in trans to potentiate the inhibitory activity of Tim-3. Up regulated in primary melanoma, it is associated with poor prognosis for survival and increased invasive behavior [5]. CEACAM-1 also increases on IL-2 activated CD56hi NK cells [6] and functions to inhibit cytolytic activity after exposure to CEACAM-1-bearing tumor cells [7]. Here we first show high expression of short cytoplasmic Ceacam-1 isoform in the human melanoma cell lines m44 and Gmel. Interestingly, we found that similar to TGFb exposed NK cells, Gmel co-cultured NK cells also displayed clear signals of exhaustion such as significant loss of cytotoxic activity and reduced IFN-g production following IL-12 stimulation. Indicating the ability of tumors to suppress NK cells driven anti-tumor activity. This approach will be useful for gaining insight into mechanisms of NK cell exhaustion induced by melanoma cells