AI Article Synopsis
- Clinical trials show that CXCR4 antagonists make immunotherapy more effective for various cancers, though the exact mechanism is still unclear.
- Researchers found that CXCR4 is a key marker in CD8 T cells, particularly in exhausted T cells, and blocking CXCR4 can reduce this exhaustion effect in vivo.
- The study uncovered that blocking CXCR4 influences the JAK2-STAT3 pathway and indicates that combining CXCR4 antagonists with immunotherapy could improve treatment outcomes, especially in patients with specific T cell profiles.
Article Abstract
Evidence from clinical trials suggests that CXCR4 antagonists enhance immunotherapy effectiveness in several cancers. However, the specific mechanisms through which CXCR4 contributes to immune cell phenotypes are not fully understood. Here, we employed single-cell transcriptomic analysis and identified CXCR4 as a marker gene in T cells, with CD8PD-1 exhausted T (T) cells exhibiting high CXCR4 expression. By blocking CXCR4, the T phenotype was attenuated in vivo. Mechanistically, CXCR4-blocking T cells mitigated the T phenotype by regulating the JAK2-STAT3 pathway. Single-cell RNA/TCR/ATAC-seq confirmed that Cxcr4-deficient CD8 T cells epigenetically mitigated the transition from functional to exhausted phenotypes. Notably, clinical sample analysis revealed that CXCR4CD8 T cells showed higher expression in patients with a non-complete pathological response. Collectively, these findings demonstrate the mechanism by which CXCR4 orchestrates CD8 T cells and provide a rationale for combining CXCR4 antagonists with immunotherapy in clinical trials.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11602566 | PMC |
| http://dx.doi.org/10.1016/j.xgen.2024.100659 | DOI Listing |
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