Dynamics of T-cell infiltration during the course of ovarian cancer: the gradual shift from a Th17 effector cell response to a predominant infiltration by regulatory T-cells
Language English Country United States Media print-electronic
Document type Journal Article, Research Support, Non-U.S. Gov't
PubMed
22865582
DOI
10.1002/ijc.27759
Knihovny.cz E-resources
- MeSH
- Cell Growth Processes immunology MeSH
- Th17 Cells immunology metabolism MeSH
- CD8-Positive T-Lymphocytes immunology metabolism pathology MeSH
- Chemokine CCL22 immunology metabolism MeSH
- Dendritic Cells immunology metabolism MeSH
- Adult MeSH
- Interferon-gamma immunology metabolism MeSH
- Middle Aged MeSH
- Humans MeSH
- Macrophages immunology metabolism MeSH
- Monocytes immunology metabolism MeSH
- Cell Line, Tumor MeSH
- Tumor Microenvironment immunology MeSH
- Ovarian Neoplasms immunology metabolism pathology MeSH
- Disease Progression MeSH
- Receptors, CCR4 immunology metabolism MeSH
- T-Lymphocytes, Regulatory immunology metabolism MeSH
- Aged, 80 and over MeSH
- Aged MeSH
- Lymphocytes, Tumor-Infiltrating immunology metabolism pathology MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Aged, 80 and over MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- CCL22 protein, human MeSH Browser
- CCR4 protein, human MeSH Browser
- Chemokine CCL22 MeSH
- Interferon-gamma MeSH
- Receptors, CCR4 MeSH
The type of immune cells that are present within the tumor microenvironment can play a crucial role in the survival of patients. However, little is known about the dynamics of the tumor-infiltrating immune cells during disease progression. We studied the immune cells that infiltrated the tumor tissues of ovarian cancer patients at different stages of disease. The early stages of development of ovarian carcinomas were characterized by a strong Th17 immune response, whereas in stage II patients, recruitment of high numbers of Th1 cells was observed. In disseminated tumors (Stages III-IV), we detected a dominant population of Helios(+) activated regulatory T cells (Tregs) along with high numbers of monocytes/macrophages and myeloid dendritic cells (mDCs). Tumor-infiltrating Tregs had markedly lower expression of CCR4 than circulating Tregs, and the numbers of tumor-infiltrating Tregs significantly correlated with the levels of CCL22 in ovarian tumor cell culture supernatants, suggesting their recruitment via a CCR4/CCL22 interaction. CCL22 was mainly produced by tumor cells, monocytes/macrophages and mDCs in the primary ovarian tumors, and its expression markedly increased in response to IFNγ. Taken together, the specific recruitment of Tregs, probably triggered by inflammatory stimuli, leads to a significant immune suppression in the advanced stages of ovarian cancer.
References provided by Crossref.org
Immunological configuration of ovarian carcinoma: features and impact on disease outcome
Immunological Network in Head and Neck Squamous Cell Carcinoma-A Prognostic Tool Beyond HPV Status
