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ILC2-derived IL-9 inhibits colorectal cancer progression by activating CD8+ T cells
Jie Wan1, Yinqiu Wu2, Lan Huang3
1The Central Laboratory, The Fourth Affiliated Hospital of Jiangsu University, Zhenjiang, 212001, China; Department of Immunology, Jiangsu University, Zhenjiang, 212013, China.
Abstract:
Group 2 innate lymphoid cells (ILC2s), characterized by secretion of type 2 cytokines, regulate multiple immune responses. ILC2s are found in different tumor tissues, and ILC2-derived interleukin (IL)-4, IL-5, and IL-13 act on the cells in tumor microenvironment to participate in tumor progression. ILC2s are abundant in colorectal cancer (CRC) tissue, but the role of ILC2s in CRC remains unclear. In this study, we found that the percentage of ILC2s was higher in CRC tissue than in the adjacent normal tissue and that these ILC2s were the dominant IL-9-secreting cell-subsets in CRC tissue, as shown by flow cytometry analysis. ILC2s-derived IL-9 could activate CD8+ T cells to inhibit tumor growth, while anti-IL-9 reversed this effect. In vivo experiments showed that neutralizing ILC2s promoted tumor growth, while tumor inhibition occurred by intravenous injection of IL-9. In conclusion, our results demonstrated that ILC2-derived IL-9 could activate CD8+ T cells to promote anti-tumor effects in CRC.
Insights
Group 2 innate lymphoid cells (ILC2s) in colorectal cancer (CRC) secrete interleukin-9 (IL-9). This IL-9 activates CD8+ T cells, promoting anti-tumor immunity and inhibiting CRC growth.
Area of Science:
- Immunology
- Oncology
Background:
- Group 2 innate lymphoid cells (ILC2s) secrete type 2 cytokines and influence immune responses.
- ILC2s are present in tumor tissues and can impact tumor progression.
- The specific role of ILC2s in colorectal cancer (CRC) remains largely undetermined.
Purpose of the Study:
- To investigate the role and function of ILC2s in colorectal cancer.
- To identify the specific cytokines secreted by ILC2s within the CRC tumor microenvironment.
- To elucidate the mechanism by which ILC2s influence tumor growth in CRC.
Main Methods:
- Flow cytometry analysis to quantify ILC2 percentages and cytokine production in CRC tissues.
- In vitro experiments to assess the effects of ILC2-derived cytokines on CD8+ T cells.
- In vivo studies using ILC2 neutralization and IL-9 administration to evaluate tumor growth modulation.
Main Results:
- ILC2s were found at higher percentages in CRC tissues compared to adjacent normal tissues.
- ILC2s in CRC tissues were identified as the primary source of IL-9 secretion.
- ILC2-derived IL-9 was shown to activate CD8+ T cells, leading to tumor growth inhibition.
- Neutralizing ILC2s promoted tumor growth, while IL-9 administration inhibited it.
Conclusions:
- ILC2s play a significant role in the colorectal cancer microenvironment.
- ILC2-derived IL-9 is a key mediator of anti-tumor immunity in CRC.
- IL-9 activates CD8+ T cells, contributing to the suppression of colorectal cancer growth.
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