Overcoming T cell dysfunction in acidic pH to enhance adoptive T cell transfer immunotherapy.

ABSTRACT: The high metabolic activity and insufficient perfusion of tumors leads to the acidification of the tumor microenvironment (TME) that may inhibit the antitumor T cell activity. We found that pharmacological inhibition of the acid loader chloride/bicarbonate anion exchanger 2 (Ae2), with 4,4'-diisothiocyanatostilbene-2,2'-disulfonicacid (DIDS) enhancedCD4⁺ andCD8⁺ T cell function upon TCR activation in vitro, especially under low pH conditions. In vivo, DIDS administration delayed B16OVA tumor growth in immunocompetent mice as monotherapy or when combined with adoptive T cell transfer of OVA-specificT cells. Notably, genetic Ae2 silencing in OVA-specificT cells improvedCD4⁺/CD8⁺ T cell function in vitro as well as their antitum

SUBMITTER: Navarro F 

PROVIDER: S-EPMC9067511 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature