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Background Pancreatic ductal adenocarcinoma (PDAC) is characterized by a highly immunosuppressive tumor microenvironment (TME) that limits effective anti-tumor immunity and contributes to poor responses to immunotherapy. γδ T cells represent a distinct subset of T lymphocytes capable of integrating innate and adaptive immune signals. However, their abundance, transcriptional states, and regulatory pathways in PDAC remain incompletely defined. In particular, the influence of inhibitory checkpoint signaling and chemokine-mediated trafficking on γδ T-cell behavior within the PDAC TME is not fully understood.Methods We performed an integrated analysis of single-cell RNA sequencing (scRNA-seq) datasets comprising tumor and adjacent normal pancreatic tissues. After dataset integration and immune cell annotation, γδ T-cell populations were identified and analyzed to assess their abundance, transcriptional characteristics, and expression of candidate regulatory pathways. Analyses focused on inhibitory checkpoint molecules and chemokine receptor–ligand networks that may influence γδ T-cell localization and function within the TME.Results Across 39 samples (33 tumors and 6 adjacent normal tissues), γδ T cells were detectable but displayed marked inter-sample variability in abundance ( IDDF2026-ABS-0335 Figure 1. Integrated pancreatic ductal adenocarcinoma single cell atlas and cell type annotation). Differential expression analyses revealed altered expression of immune regulatory genes, including increased expression of KLRC1 (NKG2A) in tumor-associated γδ T cells and elevated epithelial expression of its ligand HLA-E, supporting the presence of a potential HLA-E–NKG2A inhibitory axis in PDAC (IDDF2026-ABS-0335 Figure 2. Immune checkpoint expression on γδ T cells from pancreatic ductal adenocarcinoma single-cell RNA sequencing datasets). In addition, γδ T cells exhibited differential expression of chemokine receptors, including CCR5 and CXCR6, while several chemokine ligands, such as CCL4, CCL5, and CXCL8, were broadly expressed within the tumor microenvironment.Conclusions These findings reveal transcriptional heterogeneity among tumor-infiltrating γδ T cells and highlight candidate regulatory pathways that may constrain their activity in PDAC. Integrated single-cell analyses provide insights into checkpoint signaling and chemokine-driven positioning of γδ T cells and may inform future strategies to enhance anti-tumor immunity in pancreatic cancer.Abstract IDDF2026-ABS-0335 Figure 1Abstract IDDF2026-ABS-0335 Figure 2