THE ROLE OF GROUP 1 INNATE LYMPHOID CELLS (ILCs) IN METASTASIS AND CANCER IMMUNO-SURVEILLANCE

Abstract

In this project, we scrutinized the role of T-box transcription factors (TF), T-bet and Eomesodermin in Natural Killer (NK) cell mediated anti-cancer response using human patient samples as well as mouse models. We noted that both these transcription factors were essential for NK cell response during cancer. In the absence of T-bet in mice, higher tumour burden as well as early death was noted. Further, T-bet lacking NK cells produced less IFNγ and showed reduced cytotoxicity in vitro compared to T-bet sufficient NK cells. Similar to T-bet, Eomesodermin downregulation was associated to a lesser cytotoxic state of murine NK cells. This was checked using cell surface profiling as well as adoptive transfer experiments. Parallel studies using cancer patient samples indicated decrease in protein levels with increase in cancer stage, thereby confirming our findings and suggesting protective role of these TFs in anti-cancer response.