Dataset Information

The Trinity: Interplay among Cancer Cells, Fibroblasts, and Immune Cells in Pancreatic Cancer and Implication of CD8⁺ T Cell-Orientated Therapy.

ABSTRACT: The microenvironment in tumors is complicated and is constituted by different cell types and stromal proteins. Among the cell types, the abundance of cancer cells, fibroblasts, and immune cells is high and these cells work as the "Trinity" in promoting tumorigenesis. Although unidirectional or bidirectional crosstalk between two independent cell types has been well characterized, the multi-directional interplays between cancer cells, fibroblasts, and immune cells in vitro and in vivo are still unclear. We summarize recent studies in addressing the interaction of the "Trinity" members in the tumor microenvironment and propose a functional network for how these members communicate with each other. In addition, we discuss the underlying mechanisms mediating the interplay. Moreover, correlations of the alterations in the distribution and functionality of cancer cells, fibroblasts, and immune cells under different circumstances are reviewed. Finally, we point out the future application of CD8⁺ T cell-oriented therapy in the treatment of pancreatic cancer.

SUBMITTER: Hung YH

PROVIDER: S-EPMC9026398 | biostudies-literature | 2022 Apr

REPOSITORIES: biostudies-literature

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Publications

The Trinity: Interplay among Cancer Cells, Fibroblasts, and Immune Cells in Pancreatic Cancer and Implication of CD8<sup>+</sup> T Cell-Orientated Therapy.

Hung Yu-Hsuan YH Chen Li-Tzong LT Hung Wen-Chun WC

Biomedicines 20220418 4

The microenvironment in tumors is complicated and is constituted by different cell types and stromal proteins. Among the cell types, the abundance of cancer cells, fibroblasts, and immune cells is high and these cells work as the "Trinity" in promoting tumorigenesis. Although unidirectional or bidirectional crosstalk between two independent cell types has been well characterized, the multi-directional interplays between cancer cells, fibroblasts, and immune cells in vitro and in vivo are still u ...[more]

PMID: 35453676

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Project description:BackgroundThe role of CD161 expression on CD8+ T cells in tumor immunology has been explored in a few studies, and the clinical significance of CD161+CD8+ T cells in pancreatic ductal adenocarcinoma (PDAC) remains unclear. This study seeks to clarify the prognostic value and molecular characteristics linked to CD161+CD8+ T cell infiltration in PDAC.MethodsThis study included 186 patients with confirmed PDAC histology after radical resection. CD161+CD8+ T cell infiltration was assessed using immunofluorescence staining on tumor microarrays. Flow cytometry and single-cell RNA sequencing were used to evaluate their functional status.ResultsWe observed significant associations between tumor-infiltrating CD161+CD8+ T cells and clinicopathological factors, such as tumor differentiation, perineural invasion, and serum CA19-9 levels. Patients with higher tumor-infiltrating CD161+CD8+ T cell levels had longer overall survival (OS) and recurrence-free survival (RFS) than those with lower levels. Multivariable analysis confirmed tumor-infiltrating CD161+CD8+ T cell as an independent prognostic indicator for both OS and RFS. Notably, a combination of tumor-infiltrating CD161+CD8+ T cell and CA19-9 levels showed a superior power for survival prediction, and patients with low tumor-infiltrating CD161+CD8+ T cell and high CA19-9 levels had the worst survival. Furthermore, lower tumor-infiltrating CD161+CD8+ T cells were associated with a better response to adjuvant chemotherapy. Finally, we identified tumor-infiltrating CD161+CD8+ T cells as a unique subtype of responsive CD8+ T cells characterized by increased levels of cytotoxic cytokines and immune checkpoint molecules.ConclusionCD161+CD8+ T cells exhibit elevated levels of both cytotoxic and immune-checkpoint molecules, indicating as a potential and attractive target for immunotherapy. The tumor-infiltrating CD161+CD8+ T cell is a valuable and promising predictor for survival and therapeutic response to adjuvant chemotherapy in PDAC. Further research is warranted to validate its role in the risk stratification and optimization of therapeutic strategies.

Dataset Information

The Trinity: Interplay among Cancer Cells, Fibroblasts, and Immune Cells in Pancreatic Cancer and Implication of CD8⁺ T Cell-Orientated Therapy.

Publications

The Trinity: Interplay among Cancer Cells, Fibroblasts, and Immune Cells in Pancreatic Cancer and Implication of CD8<sup>+</sup> T Cell-Orientated Therapy.

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Dataset Information

The Trinity: Interplay among Cancer Cells, Fibroblasts, and Immune Cells in Pancreatic Cancer and Implication of CD8+ T Cell-Orientated Therapy.

Publications

The Trinity: Interplay among Cancer Cells, Fibroblasts, and Immune Cells in Pancreatic Cancer and Implication of CD8<sup>+</sup> T Cell-Orientated Therapy.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

The Trinity: Interplay among Cancer Cells, Fibroblasts, and Immune Cells in Pancreatic Cancer and Implication of CD8⁺ T Cell-Orientated Therapy.