Acquired resistance during adoptive cell therapy by transcriptional silencing of immunogenic antigens.

ABSTRACT: Immunotherapies such as adoptive cell therapy (ACT) are promising treatments for solid cancers. However, relapsing disease remains a problem and the molecular mechanisms underlying resistance are poorly defined. We postulated that the deregulated epigenetic landscape in cancer cells could underpin the acquisition of resistance to immunotherapy. To address this question, two preclinical models of ACT were employed to study transcriptional and epigenetic regulatory processes within ACT-treated cancer cells. In these models ACT consistently causes robust tumor regression, but resistance develops and tumors relapse. We identified down-regulated expression of immunogenic antigens at the mRNA level correlated with escape from immune control. To determine whether this down-regulation was under ep

SUBMITTER: Wylie B 

PROVIDER: S-EPMC6682399 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature