M6A RNA methyltransferases Mettl3/14 regulate immune responses to anti-PD-1 therapy

ABSTRACT: An impressive clinical success has been observed in treating a variety of cancers using immunotherapy with programmed cell death-1 (PD-1) checkpoint blockade. However, limited response in most patients treated with anti-PD-1 antibodies remains a challenge, requiring better understanding of molecular mechanisms limiting immunotherapy. In colorectal cancer (CRC) resistant to immunotherapy, mismatch-repair-proficient or microsatellite instability-low (pMMR-MSI-L) tumors have low mutation burden and constitute ~85% of patients. Here, we show that inhibition of N6-methyadenosine (m6A) mRNA modification by depletion of methyltransferases, Mettl3 and Mettl14, enhanced response to anti-PD-1 treatment in pMMR-MSI-L CRC and melanoma. Mettl3 or Mettl14 deficient tumors increased cytotoxic tumor-infil

SUBMITTER: Prof. Tariq, M Rana 

PROVIDER: S-SCDT-EMBOJ-2020-104514 | biostudies-other |

REPOSITORIES: biostudies-other