ROLE OF INNATE CD8+ T CELLS IN CANCER

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

Buenos Aires

Congreso; JOINT MEETING OF BIOSCIENCE SOCIETIES; 2017

Innate CD8+ T cells were discovered about 10 years ago. Thesecells have particular phenotypic features (CD44hi CD122hi CD49dhi)and exert cytotoxic activity mainly through NKG2D expression withoutspecific antigen recognition. Innate CD8+ T cells express highlevels of the transcription factor Eomesodermin and low expressionof T-bet. They rapidly produce IFNg after IL-12 and IL-18 stimulationdue to constitutive expression of their receptors. Moreover, an antitumorrole of innate CD8+ cells has been recently postulated bothin mice and human. Our experiments using murine tumor cell linesdemonstrate that systemic expression of these 2 cytokines (by hydrodynamicinjection of their cDNAs) significantly attenuate tumorgrowth in WT mice compared to control group (injected with an emptycDNA) (p<0.05). Phenotypic analysis (based on the mentionedmarkers) of splenocytes and tumor-draining lymph node showed anincrease of innate CD8+ cells in 12+18-treated mice compared tocontrol group in both WT and OT-I mice (p<0.05).Several chemokines and their receptors have been described toparticipate in the homing of different immune cells to tumors. Betweenthem, CCR5 seems to be quite important for T cell extravasation.When we analyzed the expression of CCR5, we observed anincrement in CCR5+ CD8+ but not in CD4+ T cells (by flow cytometry)only in mice treated with IL-12+IL-18 cDNAs compared to controlmice (p<0.05). Accordingly, preliminary flow cytometry data revealedan increase in Percoll purified-infiltrating innate CCR5+ CD8+ T cellsinto B16 tumors of 12+18-treated mice compared to control groupthat correlates with an increase of total CD45+ cells infiltrating B16tumor of 12+18-treated mice (microscopic analysis by immune fluorescence).All together this data suggest that innate CD8+ cells may have acritical role in the control of tumor growth that could be importantwhen TCR specific immune response is bypassed by tumors thatdown-regulates MHC-I expression.