Role of Ahr and Hif1a in the suppressive ability of Regulatory T cells

Chronic Lymphocytic Leukemia (CLL) represents the most frequent leukemia in adults and it is considered a deadly incurable disease. It is characterized by an accumulation of abnormal B lymphocytes in the blood and lymphoid organs of patients. As it is widely enstablished, CLL progression is highly dependent on complex interactions between tumor cells and a milieu of accessory cells collectivelly known as the tumor microenvironment (TME). Indeed, CLL cells can modify stromal cells and immune cells to promote the survival of the leukemic clone and to escape from the immune system surveillance. Within the TME, regulatory T cells (Tregs) represent a subtype of CD4 + T cells with immunosuppressive abilities that inhibit the functions of antigen presenting cells and effector T cells, causing the evasion of cancer cells from the immune control. The aim of the present study is to investigate the role of two transcription factors, Ahr and Hif1α, in the suppressive ability of Tregs during CLL development. To this aim, conditional knock out mice lacking the two genes were generated and we could observe that the absence of Ahr and Hif1α in Tregs has an impact on the suppressive abilities of these cell type both in vivo and ex vivo.

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