ROLE AND REGULATION OF HUMAN INNATE LYMPHOID CELLS AND NATURAL KILLER CELLS IN LYMPHOMA

Innate immune system can be helpful or harmful in cancer regression depending on tumor microenvironment. Innate lymphoid cells are constituents of innate immune system with helper innate lymphoid cells (ILCs) that are mainly tissue-resident lymphocytes and natural killer cells (NK) that are pro-inflammatory cells displaying cytotoxic activity. In our project, we explored the role and regulation of helper ILCs and NK cells in B-cell non-Hodgkin lymphoma and Hodgkin lymphoma, hematologic malignancies derived from B-lymphocytes. We found that in peripheral blood of non-Hodgkin lymphoma patients, helper ILCs showed higher expression of activation markers compared to healthy donors while NK cells show a potential pro-tumour role. Moreover, analysing patients’ plasma we observed some upregulated chemokines and cytokines compared to healthy donors. We performed in vitro mixed lymphocyte-tumour cell cultures of peripheral blood mononuclear cells (PBMCs) from healthy donors and lymphoma cell lines, using healthy B-lymphocytes and PBMCs grown alone as controls. Our experiments showed a contact dependent downregulation of activation markers on helper ILCs in presence of tumour cells. However, in absence of all other immune cells, ILCs showed high cell activation and cytokine production in presence of lymphoma cell lines, thus meaning that among the immune cells there is a cell family able to counteract the ILC activity, thus contributing potentially to the formation of an immunosuppressive environment. We suggested that T regulatory cells are at the base of this mechanism since their removal from PBMCs resulted in a rescue of ILC cytotoxic potential. Altogether, these data suggest a mechanism of innate lymphoid cell regulation that could become a new possible therapeutic strategy for non-Hodgkin lymphoma patients. In parallel, we also investigate the phenotype and distribution of ILCs and NK in Hodgkin lymphoma. Results show that in HL, ILCs were increased compared to healthy donors, in particular ILC1. Moreover, patient circulating ILCs express higher level of granzyme B and perforin. These preliminary data suggest an involvement of ILCs in HL biology.