| First Author | Swaminathan S | Year | 2020 |
| Journal | Nat Commun | Volume | 11 |
| Issue | 1 | Pages | 2860 |
| PubMed ID | 32503978 | Mgi Jnum | J:291910 |
| Mgi Id | MGI:6447057 | Doi | 10.1038/s41467-020-16447-7 |
| Citation | Swaminathan S, et al. (2020) MYC functions as a switch for natural killer cell-mediated immune surveillance of lymphoid malignancies. Nat Commun 11(1):2860 |
| abstractText | 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 SRalpha-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 patients, low expression of both STAT1 and STAT2 correlates significantly with the absence of activated NK cells and predicts unfavorable clinical outcomes. Our studies thus provide a rationale for developing NK cell-based therapies to effectively treat MYC-driven lymphomas in the future. |
