M⁶ A 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 -methyladenosine (m⁶ A) 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 incre

SUBMITTER: Wang L 

PROVIDER: S-EPMC7560214 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature