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In Vivo Augmentation of Gut-Homing Regulatory T Cell Induction
Published on: January 22, 2020
Colorectal cancer-derived Foxp3(+) IL-17(+) T cells suppress tumour-specific CD8+ T cells
1Section of Surgery, Cancer Center, The Fourth Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, China.
Abstract:
The pathogenesis of cancer is remained to be further understood. This study aims to investigate the role of tumour-derived Foxhead box P3 (Foxp3)(+) interleukin (IL)-17(+) T cells on suppressing tumour-specific CD8(+) T cells. Colorectal cancer (CRC) tissue was collected from surgically removed cancer tissue of 22 patients with CRC. Foxp3(+) IL-17(+) T cells in cancer tissue were examined by flow cytometry. A set of cell markers and cytokines expressed by Foxp3(+) IL-17(+) T cells were determined by immune staining. By coculture with isolated peripheral CD8(+) T cells, the immune regulatory capacity of Foxp3(+) IL-17(+) T cells was examined. The results showed that a number of Foxp3(+) IL-17(+) T cells were found in CRC tissue (22.8 ± 2.6 cells/mm(2) tissue) that was significantly more than in non-cancer colonic mucosa (5.6 ± 1.04 cells/mm(2) tissue). The Foxp3(+) IL-17(+) cells also CD4(+), CCR6(+), transforming growth factor (TGF)-beta(+) and IL-6(+) . The CD8(+) T cells proliferated markedly after exposure to tumour protein in culture that was suppressed in the presence of CRC-derived Foxp3(+) IL-17(+) T cells; the suppression was attenuated by pretreatment with anti-IL-17 antibody. We conclude that CRC-derived Foxp3(+) IL-17(+) T cells have the ability to suppress tumour-specific CD8(+) T cells. This subset of T cells may be a novel therapeutic target in the treatment of CRC.
Insights
Tumour-derived Foxhead box P3 (Foxp3)(+) interleukin (IL)-17(+) T cells suppress anti-cancer CD8(+) T cells in colorectal cancer. These cells represent a potential new therapeutic target for CRC treatment.
Area of Science:
- Immunology
- Oncology
- Cell Biology
Background:
- The intricate mechanisms of cancer pathogenesis require further elucidation.
- Understanding immune cell interactions within the tumour microenvironment is crucial for developing effective cancer therapies.
Purpose of the Study:
- To investigate the role of tumour-infiltrating Foxhead box P3 (Foxp3)(+) interleukin (IL)-17(+) T cells in suppressing tumour-specific CD8(+) T cell responses in colorectal cancer (CRC).
Main Methods:
- Colorectal cancer tissues from 22 patients were analyzed using flow cytometry and immune staining to identify and characterize Foxp3(+) IL-17(+) T cells.
- Peripheral CD8(+) T cells were co-cultured with CRC-derived Foxp3(+) IL-17(+) T cells to assess immune regulatory capacity.
Main Results:
- Foxp3(+) IL-17(+) T cells were significantly more abundant in CRC tissue compared to non-cancerous colonic mucosa.
- These cells expressed CD4, CCR6, transforming growth factor-beta (TGF-β), and IL-6.
- CRC-derived Foxp3(+) IL-17(+) T cells suppressed the proliferation of tumour-specific CD8(+) T cells, an effect partially reversed by anti-IL-17 antibody treatment.
Conclusions:
- Tumour-associated Foxp3(+) IL-17(+) T cells exhibit immunosuppressive properties against tumour-specific CD8(+) T cells in colorectal cancer.
- This T cell subset presents a potential novel therapeutic target for enhancing anti-tumour immunity in CRC.
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