Abstract
<div>Abstract<p>In pancreatic ductal adenocarcinoma, the infiltration of CD8<sup>+</sup> T cells within the tumor microenvironment correlates with a favorable prognosis. However, a significant proportion of tumor-infiltrating T cells become trapped within the desmoplastic stroma and lack tumor reactivity. Here, we explored different T-cell subsets in pancreatic tumors and adjacent tissues. We identified a subset of CD8<sup>+</sup> T cells, double positive (DP) for CD39 and CD103 in pancreatic tumors, which has recently been described to display tumor reactivity in other types of solid tumors. Interestingly, DP CD8<sup>+</sup> T cells preferentially accumulated in central tumor tissues compared with paired peripheral tumor and adjacent non-tumor tissues. Consistent with an antigen encounter, DP CD8<sup>+</sup> T cells demonstrated higher proliferative rates and displayed an exhausted phenotype, characterized by elevated expression of PD-1 and TIM-3, compared with CD39<sup>−</sup>CD103<sup>−</sup> CD8<sup>+</sup> T cells. In addition, DP CD8<sup>+</sup> T cells exhibited higher expression levels of the tissue trafficking receptors CCR5 and CXCR6, while displaying lower levels of CXCR3 and CXCR4. Importantly, a high proportion of DP CD8<sup>+</sup> T cells is associated with increased patient survival. These findings suggest that DP CD8<sup>+</sup> T cells with a phenotype reminiscent of that of tumor-reactive T cells are present in pancreatic tumors. The abundance of DP CD8<sup>+</sup> T cells could potentially aid in selecting patients for pancreatic cancer immunotherapy trials.</p>Significance:<p>Patients with pancreatic cancer with a high proportion of CD39<sup>+</sup>CD103<sup>+</sup> CD8<sup>+</sup> T cells exhibiting a tumor-reactive phenotype have improved survival rates, suggesting their potential utility in selecting candidates for immunotherapy trials.</p></div>
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