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Tailoring In Vivo Cytotoxicity Assays to Study Immunodominance in Tumor-specific CD8+ T Cell Responses
Published on: May 6, 2019
Human activated T lymphocytes modulate IDO expression in tumors through Th1/Th2 balance
Jessica Godin-Ethier1, Sandy Pelletier, Laïla-Aïcha Hanafi
1Research Centre, Centre Hospitalier de l'Université de Montréal-Hôpital Notre-Dame, Université de Montréal and Institut du Cancer de Montréal, Montreal, Quebec, Canada.
Journal of Immunology (Baltimore, Md. : 1950)
|November 26, 2009
Summary
Tumors can suppress immune responses by producing indoleamine 2,3-dioxygenase (IDO). Activated T cells induce IDO in tumor cells, but Th2 cytokines can inhibit it, revealing complex immune regulation in cancer.
Area of Science:
- Immunology
- Cancer Biology
- Tumor Microenvironment
Background:
- Cancer vaccines often fail to induce tumor regression despite generating immune responses.
- Tumors may evade immune detection by producing immunosuppressive molecules like indoleamine 2,3-dioxygenase (IDO).
- Mechanisms regulating IDO expression in tumor cells are not fully understood.
Purpose of the Study:
- To investigate how activated T cells and cytokines regulate IDO expression in tumor cells.
- To examine the presence and regulation of IDO in human breast and kidney carcinomas.
- To understand the complex immune interactions within the tumor microenvironment.
Main Methods:
- In vitro co-culture of activated T cells with breast and kidney tumor cell lines.
- Analysis of IDO expression in response to T cell activation and cytokines (IFN-gamma, IL-13).
- Immunohistochemical analysis of IDO expression and T cell infiltration in human tumor samples.
Main Results:
- Activated T cells induce functional IDO expression in tumor cell lines, partly mediated by IFN-gamma.
- The Th2 cytokine IL-13 negatively modulates IDO expression.
- IDO is expressed in most breast and kidney carcinoma samples, with infiltrating activated Th1-polarized T cells.
Conclusions:
- Tumor cells can be induced to express immunosuppressive IDO by activated T cells.
- Immune activity within tumors is complex, involving both pro- and anti-inflammatory signals.
- Future cancer immunotherapies must address tumor-induced immunosuppression, including IDO regulation.
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