ArticleAmerican journal of clinical oncology2026
Relevance of Chemokines in Mobilizing γδ T Cells in the Biliary Tract Cancer Microenvironment: Potential for γδ T-Cell-Based Adoptive Cell Therapy.
Article in American journal of clinical oncology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.
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1 citing paper in PubMed.
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4 authors.
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Abstract
objectiveBiliary tract cancer (BTC) has a poor prognosis with limited therapeutic options. γδ T cells represent an MHC-independent immune cell population; however, their therapeutic efficacy in solid tumors is constrained by insufficient tumor infiltration. Chemokine-mediated trafficking is fundamental to T lymphocyte recruitment; however, the chemokine landscape of the BTC tumor microenvironment (TME) remains uncharacterized. Using single-cell RNA sequencing of BTC tissues, we delineated chemokine ligand expression patterns, stratified chemokine producers by lineage, assessed γδ T-cell recruitment mechanisms, and identified chemokine-mediated immune escape.
methodsWe analyzed single-cell RNA sequencing data from 3 independent GEO cohorts (GSE210066, GSE201425, and GSE213452; 19 patients) to comprehensively delineate γδ T-cell mobilization-related chemokine expression across the BTC TME using the Seurat v5.0 pipeline in R.
resultsAnalysis identified a multiaxis chemokine profile within the BTC TME. High expression of CCL5, CCL4, and CCL3 established predominant CCR5-mediated recruitment axes supporting Vγ9Vδ2 T-cell infiltration, whereas CCL2 and modest CXCL8 supported CCR2+ and CXCR1+ Vδ1 T-cell recruitment. Notably, CXCL16 expression supported epithelial γδ T-cell homing through CXCR6. However, critical deficiencies in CXCL9 and CXCL10 suppress the IFN-γ-driven immunity. Paradoxically, chemokine axes supporting γδ T-cell recruitment (CCL2-CCR2, CXCL8-CXCR1, CXCL12-CXCR4) simultaneously recruit immunosuppressive populations, such as myeloid-derived suppressor cells (MDSCs), regulatory T cells (Tregs), and tumor-associated macrophages (TAMs).
conclusionComprehensive single-cell analysis identified selective chemokine recruitment signatures supporting γδ T-cell infiltration but revealed paradoxical corecruitment of immunosuppressive populations. Patient stratification through chemokine profiling, combined with γδ T-cell enrichment and targeted chemokine antagonism, represents a rational therapeutic strategy.
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