Targeting sphingosine 1-phosphate receptor 3 inhibits T-cell exhaustion and regulates recruitment of proinflammatory macrophages to improve antitumor efficacy of CAR-T cells against solid tumor.

ABSTRACT:

Backgrounds

Chimeric antigen receptor (CAR)-modified T cells (CAR-T) are limited in solid tumors due to the hostile tumor microenvironment (TME). Combination therapy could be a promising approach to overcome this obstacle. Recent studies have shown that sphingosine 1-phosphate receptor (S1PR)3 has tremendous potential in regulating the immune environment. However, the functional significance of S1PR3 in T-cell-based immunotherapies and the molecular mechanisms have not been fully understood.

Methods

Here, we studied the combination of EpCAM-specific CAR T-cell therapy with pharmacological blockade of S1PR3 against solid tumor. We have applied RNA sequencing, flow cytometry, ELISA, cellular/molecular immunological technology, and mouse models of solid cancers.

Results

SUBMITTER: Gao G 

PROVIDER: S-EPMC10441059 | biostudies-literature | 2023 Aug

REPOSITORIES: biostudies-literature