figure
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 Effects of presurgical chemotherapy on the immune landscape. The immune landscape for patients that underwent upfront surgery (gray squares) was compared with the patients that underwent neoadjuvant chemotherapy followed by surgery (white squares). A, Kaplan–Meier survival curves comparing the two groups. B, Proportion of CD39+ CD103+ CD8+ T cells. C, Left, Proportion of CD4+ and CD8+ T cells out of CD45+ cells. Right, Ratio of cells in central tissues relative to peripheral and non-tumor tissues for CD4+ and CD8+ T cells out of CD45+ cells. Proportion of CD4+ T cells (D) and CD8+ T cells (E) expressing PD-1, TIM-3, CCR5, CXCR4, CXCR5, and CXCR3. F, Left, Proportion of CD19+ cells out of CD45+ cells. Right, Proportion of CD19 cells in central tissues relative to peripheral and non-tumor tissues. Mann–Whitney U test was used to detect statistically significant differences. *, P < 0.05; **, P < 0.01; ***, P < 0.001; ns, not significant.
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.
