Single-cell RNA-seq and spatial transcriptomics characterize CD8⁺ exhausted T cells in pancreatic ductal adenocarcinoma.

Authors

Jing Mao, Chenxin Yan, Ying Mei, Yanjun Yao, Xingxia Yang, Jing Zhuang, Kuai Yu, Gangzhao Gu, Hengzhi Zhang, Yu Zheng, Yunyao Wei, Shuwen Han, Qiang Yan

Published in

iScience. Volume 29. Issue 8. Pages 116934. Aug 21, 2026. Epub Jul 27, 2026.

Abstract

Pancreatic cancer resists immunotherapy due to a suppressive immune microenvironment where CD8⁺ T cells play a key role. Using single-cell RNA sequencing and spatial transcriptomics, we characterized CD8⁺ exhausted T (Tex) cells in pancreatic ductal adenocarcinoma (PDAC). We generated single-cell profiles from PDAC tumors and matched peripheral blood mononuclear cells, and performed T cell sub-analysis. We found CXCL13 upregulated and GZMK downregulated in CD8⁺ Tex cells. Cell-cell interaction analysis showed that T cells most frequently interacted with myeloid cells and cancer cells via ligand-receptor pairs; INHBA⁺ macrophages and cancer cells communicated most with CD8⁺ Tex cells. Two key LR pairs (SPP1-integrin α4β1 and PLAUR-integrin α4β1) mediated crosstalk between cancer cells and CD8⁺ Tex cells, confirmed by immunofluorescence, spatial mapping, and protein docking. High SPP1 and PLAUR expression correlated with poor prognosis in TCGA-PAAD. These findings provide a resource for understanding CD8⁺ T cell exhaustion in PDAC.

PMID:
42548877
Bibliographic data and abstract were imported from PubMed on 04 Aug 2026.

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