Dampening of cytotoxic innate lymphoid cells: A new tumour immune escape mechanism in B cell non-Hodgkin's lymphoma.

The role and regulation of innate immune cells is poorly understood in B-cell non-Hodgkin lymphoma (NHL). As natural killer (NK) cells, helper innate lymphoid cells (ILCs) are lymphocytes endowed with either anti- or pro-tumour activity and involved in inflammatory processes. In our ex vivo analysis of NK cells and ILCs from NHL patients, we observed that, in comparison to healthy donors (HD), the frequency of the cytotoxic subset of NK cells, the CD16+ NK, decreased in patients' peripheral blood. In general, circulating NK cells showed a pro-tumorigenic phenotype, while ILCs displayed a more activated/cytotoxic phenotype. Conversely, at the tumour site, in patients' lymph nodes, ILCs showed a low expression of granzyme.In vitromixed lymphocyte-tumour cell cultures with HD PBMCs and NHL cell lines demonstrated that ILC cytotoxic potential was lowered by the presence of tumour cells but, in the absence of T regulatory cells (Tregs), their cytolytic potential was recovered. Our data shed novel light on dysfunctional innate immunity in NHL. We suggest a new mechanism of tumour immuno-escape based on the reduction of cell cytotoxicity involving ILCs and likely controlled by Tregs.