New insights in the generation and antitumoral effects of Ag-inexperienced memory CD8+ T cells

Tucumán

Congreso; LXVII Reunión Científica Anual de la Sociedad Argentina de Inmunología (SAI); 2019

Sociedad Argentina de Inmunología (SAI)

Ag-inexperienced memory CD8+ T cells (AIM) are a subset of T lymphocytes with particular phenotypic features (CD44hi CD122hi CD49dlo Eomeshi Tbetlo) and the ability to rapidly produce IFNalpha after IL-12+IL-18 stimulation. An antitumor role of AIM has been recently postulated both in mice and in humans. Our experiments using murine tumor cell lines demonstrate that systemic expression of IL-12+IL-18 in OT-I mice (by hydrodynamic injection of its cDNAs) significantly increased the number of AIM in SLO (spleen and lymph nodes) and attenuates tumor growth compared to control group (injected with an empty cDNA)(p<0.05). Accordingly, an increase in the number and the activation profile of tumor infiltrating AIM (measured by Ca2+ influx) were observed in IL-12+IL-18-treated mice compared to control group suggesting that AIM could exert tumor growth control in an Ag-independent manner. Regarding their development in SLO, our data demonstrate that IL-4 KO mice did not alter the number of AIM in SLO after IL-12+IL-18 expression compared to WT mice demonstrating that generation of this population could be redundantly driven by other signals. Interestingly, IFN KO mice show both lower number and antitumor effects after IL-12+IL-18 expression (p<0.05). This result suggests that IFNalpha could be involved both generation and cytotoxic mechanisms of these cells. All together this data suggest that AIM have a critical role in tumor growth control by mechanisms that involve IFNalpha and could represent an important antitumor mechanism against cancer cells when TCR specific immune response is bypassed by down-regulation of MHC-I expression in cancer cells.