Activated Pancreatic Stellate Cells Sequester CD8+ T Cells to Reduce Their Infiltration of the Juxtatumoral Compartment of Pancreatic Ductal Adenocarcinoma
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...Powell, 2015), and (3) PDA, in which endogenous T cell responses are rare (Emmrich et al., 1998; Ene-Obong et al., 2013; von Bernstorff et al., 2001)....
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...…ovarian cancer, in which potentially beneficial T cell responses exist in a subset of patients, but have proven difficult to augment (Santoiemma and Powell, 2015), and (3) PDA, in which endogenous T cell responses are rare (Emmrich et al., 1998; Ene-Obong et al., 2013; von Bernstorff et al., 2001)....
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"Activated Pancreatic Stellate Cells..." refers background in this paper
...To our knowledge, we identified for the first time that higher CD8þ T-cell infiltration in PDAC tumors correlates with better patient survival, a finding that provides evidence for antitumor CD8þ T-cell cancer immunoediting in human PDAC.(2) The PDAC stromal microenvironment is composed of activated myofibroblasts including aPSC, extracellular matrix, blood vessels, and various immune cells, and the individual contributions to tumor progression remain elusive....
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...These findings in human PDAC compared with other PBDs, reported for the first time, are consistent with reduced infiltration of CD8þ cytotoxic T cells recently reported in the KPC mouse model of PDAC.8,22,23 B A SIC A N D TR A N SLA TIO N A L PA N C R EA S Differential Immune Cell Infiltrate in Stromal Subcompartments We next characterized the immune infiltrate within stromal subcompartments of PDAC and identified that cytotoxic effector T cells (CD8þ), Tregs (FoxP3þ), B cells (CD20þ), and natural killer cells (CD56þ) were significantly reduced in juxtatumoral compartments compared with the panstromal areas....
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...Ourdata further show for thefirst time that ahigherCD8þ T-cell juxtatumoral infiltrate is associated with improved survival postsurgical resection as analyzed by X-Tile software (Figure 3 and Supplementary Table 5).17,25 Of interest, a lower juxtatumoral Treg (FoxP3þ) infiltrate also showed a prosurvival effect in patients with PDAC....
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...To our knowledge, we identified for the first time that higher CD8þ T-cell infiltration in PDAC tumors correlates with better patient survival, a finding that provides evidence for antitumor CD8þ T-cell cancer immunoediting in human PDAC.2 The PDAC stromal microenvironment is composed of activated myofibroblasts including aPSC, extracellular matrix, blood vessels, and various immune cells, and the individual contributions to tumor progression remain elusive.26 The PDAC stroma has been classified into 2 compartments based on differential gene expression13,30: the juxtatumoral and panstromal compartments....
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...Taken together, these data suggest an important role for stromal PSC/T-cell interaction and the CXCL12/CXCR4 axis in PDAC....
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Additional excerpts
...The paucity of functional vasculature close to the PDAC tumor cells (juxtatumoral) is well established.(24) Taken together, these observations strongly suggest a hitherto unreported PDAC-specific CD8þ T-cell trafficking defect within human PDAC tissues....
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