Abstract 2885: Somatic mutation of STAT3 leads to the preferential Th17 differentiation in human nave CD4-positive cells and favor TCR-mediated proliferation

Intro: Mature Th17 lymphocytes play a key role in the host defenses against bacteria and fungi although unchecked Th17 activation can lead to autoimmune disorders, inflammation and cancer. The engagement of CD4 nave T-cells via IL6 and TGF favors a Th17 differentiation program, which requires the presence of IL21 and IL23 to reach a complete maturation and the maintenance of Th17 phenotype. The Th17 differentiation requires multiple lineage defining transcription factors (i.e. ROR, RORt, and STAT3) and the activation of STAT3 signaling, which regulates a plethora of factors (i.e. RORt, IL23R), is required for the full execution of the Th17 program. We have recently shown that JAK1STAT3 activating mutations in Anaplastic Large cell Lymphomas (ALCL) are oncogenic, but it is unknown their protumorigenic contribution in modulatingderailing the host microenviroment and the host responses.