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Supplementary Figure S4 from Exhausted Tumor-infiltrating CD39+CD103+ CD8+ T Cells Unveil Potential for Increased Survival in Human Pancreatic Cancer

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journal contribution
posted on 2024-02-19, 14:20 authored by Laia Gorchs, Carlos Fernández-Moro, Ebba Asplund, Marlies Oosthoek, Martin Solders, Poya Ghorbani, Ernesto Sparrelid, Elena Rangelova, Matthias J. Löhr, Helen Kaipe

T regulatory cells out of CD4+ and CD39+ CD4+ T cells.

Funding

Swedish Cancer Foundation

Cancerföreningen i Stockholm (Cancer Society in Stockholm)

Insamlingsstiftelsen Cancer- och Allergifonden (Cancer and Allergy Fund)

Ruth och Richard Julins Stiftelse (Ruth and Richard Julin Foundation)

History

ARTICLE ABSTRACT

In pancreatic ductal adenocarcinoma, the infiltration of CD8+ 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+ 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+ 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+ T cells demonstrated higher proliferative rates and displayed an exhausted phenotype, characterized by elevated expression of PD-1 and TIM-3, compared with CD39−CD103− CD8+ T cells. In addition, DP CD8+ 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+ T cells is associated with increased patient survival. These findings suggest that DP CD8+ T cells with a phenotype reminiscent of that of tumor-reactive T cells are present in pancreatic tumors. The abundance of DP CD8+ T cells could potentially aid in selecting patients for pancreatic cancer immunotherapy trials. Patients with pancreatic cancer with a high proportion of CD39+CD103+ CD8+ T cells exhibiting a tumor-reactive phenotype have improved survival rates, suggesting their potential utility in selecting candidates for immunotherapy trials.