T-cell Localization, Activation, and Clonal Expansion in Human Pancreatic Ductal Adenocarcinoma.

ABSTRACT: Pancreatic ductal adenocarcinoma (PDA) is a lethal malignancy resistant to most therapies, including immune checkpoint blockade. To elucidate mechanisms of immunotherapy resistance, we assessed immune parameters in resected human PDA. We demonstrate significant interpatient variability in T-cell number, localization, and phenotype. CD8⁺ T cells, Foxp3⁺ regulatory T cells, and PD-1⁺ and PD-L1⁺ cells were preferentially enriched in tertiary lymphoid structures that were found in most tumors compared with stroma and tumor cell nests. Tumors containing more CD8⁺ T cells also had increased granulocytes, CD163⁺ (M2 immunosuppressive phenotype) macrophages, and FOXP3⁺ regulatory T cells. PD-L1 was rare on tumor cells, bu

SUBMITTER: Stromnes IM 

PROVIDER: S-EPMC5802342 | biostudies-literature | 2017 Nov

REPOSITORIES: biostudies-literature