T-bet controls CD4+CD25+Foxp-3+ T regulatory cells and Th17 cells in lung adenocarcinoma (41.59)

Abstract

Abstract The range of identified effector CD4+ T cell lineages has been expanded to enclose the Th17 cells whose function in lung tumor has not been investigated yet. In this study, we report increased expression of the two newly identified transcription factors of the Th17 lineage, RORA and RORC2, in the lung of patients affected by lung adenocarcinoma. Targeting IL-17A in a murine model of lung adenocarcinoma, resulted in local expansion of CD4+ effector T cells producing IFNγ and reduction of CD4+CD25+FOXP3+ regulatory T cells. In support of a protective role of IFNγ in this model, T-bet (-/-) mice exhibited increased tumor load, decreased survival and increased residual CD4+CD25+FOXP3+ T regulatory cells after anti-IL-17A antibodies treatment as compared to wild type littermates. Thus, blockade of lung Th17 responses requires T-bet to reduce T-regulatory cells for limiting lung cancer.