MYC functions as a switch for natural killer cell-mediated immune surveillance of lymphoid malignancies.

ABSTRACT: The MYC oncogene drives T- and B- lymphoid malignancies, including Burkitt's lymphoma (BL) and Acute Lymphoblastic Leukemia (ALL). Here, we demonstrate a systemic reduction in natural killer (NK) cell numbers in SRα-tTA/Tet-O-MYC^ON mice bearing MYC-driven T-lymphomas. Residual mNK cells in spleens of MYC^ON T-lymphoma-bearing mice exhibit perturbations in the terminal NK effector differentiation pathway. Lymphoma-intrinsic MYC arrests NK maturation by transcriptionally repressing STAT1/2 and secretion of Type I Interferons (IFNs). Treating T-lymphoma-bearing mice with Type I IFN improves survival by rescuing NK cell maturation. Adoptive transfer of mature NK cells is sufficient to delay both T-lymphoma growth and recurrence post MYC inactivation. In MYC-driven BL patie

SUBMITTER: Swaminathan S 

PROVIDER: S-EPMC7275060 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature