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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
Author(s) -
Fialová Anna,
Partlová Simona,
Sojka Luděk,
Hromádková Hana,
Brtnický Tomáš,
Fučíková Jitka,
Kocián Petr,
Rob Lukáš,
Bartůňková Jiřina,
Špíšek Radek
Publication year - 2012
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.27759
Subject(s) - immune system , ovarian cancer , tumor microenvironment , biology , chemokine , immunology , ccr4 , cancer research , myeloid , infiltration (hvac) , population , cancer , medicine , chemokine receptor , thermodynamics , genetics , physics , environmental health
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.