CCR5 and IL-12 co-expression in CAR T cells improves antitumor efficacy by reprogramming tumor microenvironment in solid tumors.

ABSTRACT: Chimeric antigen receptor (CAR) T cell therapy for solid tumors faces significant challenges, including inadequate infiltration, limited proliferation, diminished effector function of CAR T cells, and an immunosuppressive tumor microenvironment (TME). In this study, we utilized The Cancer Genome Atlas database to identify key chemokines (CCL4, CCL5, and CCR5) associated with T cell infiltration across various solid tumor types. The CCL4/CCL5-CCR5 axis emerged as significantly correlated with the presence of T cells within tumors, and enhancing the expression of CCR5 in CAR T cells bolstered their migratory capacity. Furthermore, single-cell immunoprofiling of tumor tissues revealed that macrophages within the TME primarily interact with CD8⁺ T cells, impeding their tumor respons

SUBMITTER: Tian Y 

PROVIDER: S-EPMC11699016 | biostudies-literature | 2025 Jan

REPOSITORIES: biostudies-literature