"Innate CD8 T cells: an unexplored line of defense of the immune system in cancer?".

SAVID FRONTERA CONSTANZA; BAEZ NATALIA SOLEDAD; MARIA CECILIA RODRIGUEZ-GALAN

Mar del Plata

Congreso; LXI Reunión Científica Anual de la Sociedad Argentina de Investigación Clínica (SAIC); LXIV REUNIÓN ANUAL Sociedad Argentina de Inmunología; XLVIII Reunión Anual de la Sociedad Argentina de Farmacología Experimental (SAFE); 2016

Innate CD8+ T cells give rise in the thymus apart from the conventional T CD8+ development pathway. One particular marker that distinguishes CD8+innate from conventional thymocytes is high expression of CD44 similar to memory T cells in the innate subset. It has been recently demonstrated that these cells could play an important role during neoplasic processes due to their capacity to produce large amounts of interferon-gamma after interleukin 12 (IL-12) and IL-18 stimulation and their high cytotoxic activity mediated mainly by the NKG2D receptor.In our group we developed an experimental model where we induce systemic and transitory expression of IL-12 and IL-18 by hydrodynamic injection of their cDNAs. We observed that the levels of both cytokines are significantly higher in 12+18 group than control group, injected with the empty plasmid,up to 7-10 days post-treatment (p<0,05).Interestingly we foundin lymph nodes and spleen, a large number of CD8+ CD44hi T cells after IL-12 and IL-18 systemic expression (p<0,05). Moreover, these cells also express high levels of EOMES, a transcription factor characteristic of innate CD8+ T cellscompared to CD8+ CD44lo T cells (p<0,05).In vitroantitumor assays demonstrated that splenocytes from 12+18 mice, enriched in CD8+ CD44hi EOMES+ NKG2D+ T cells, kill more efficiently YAC-1 tumor cells that express ligands for NKG2D than splenocytes from control mice (p<0,05).In vivo experiments demonstrated that IL-12+IL-18 cDNA treatment significantly attenuate tumor growth in a B16 murine melanoma model measured by the size and the weight of the tumors(p<0,05).Interestingly, in the absence of CD8+ T cells (CD8KO mice), the size of the tumors is larger than in control mice after IL-12+IL-18 systemic expression.All together, our data indicates that systemic expression of IL-12 and IL-18 selectively expands a population of CD8+ T cells with an innate phenotype with a high antitumoral capacity.