Blocking CXCR4⁺ CD4⁺ T cells reprograms T_reg-mediated immunosuppression via modulating the Rho-GTPase/NF-κB signaling axis.

ABSTRACT:

Background

While clinical trials have shown that CXCR4 antagonists can enhance the efficacy of cancer immunotherapy, the molecular mechanisms by which CXCR4 modulates the tumor microenvironment remain poorly understood. We recently identified CXCR4 as a regulator of exhausted CD8⁺ T cell phenotypes in cancer. Here, we investigate its role in orchestrating regulatory T (T_reg) cell-mediated immunosuppression within tumors.

Methods

We conducted meta-analyses of single-cell RNA-seq datasets from pan-cancer tissues to characterize CXCR4 expression patterns in CD4⁺ T cells. Using CXCR4 antagonists and conditional knockout mice (Cxcr4^flox/flox, Lck^Cre), we inhibited T_reg phenotypes in vivo. Through single-cell transc

SUBMITTER: Cao C 

PROVIDER: S-EPMC12323159 | biostudies-literature | 2025 Aug

REPOSITORIES: biostudies-literature