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Identification of CD8+CD25+Foxp3+ suppressive T cells in colorectal cancer tissue
- Source :
- Gut, Gut, BMJ Publishing Group, 2009, 58 (4), pp.520-9. ⟨10.1136/gut.2008.158824⟩, Gut, 2009, 58 (4), pp.520-9. ⟨10.1136/gut.2008.158824⟩
- Publication Year :
- 2009
- Publisher :
- HAL CCSD, 2009.
-
Abstract
- International audience; BACKGROUND: The antitumoral immune response is one determinant of colorectal cancer (CRC) outcome. Recent work suggests that Foxp3(+)CD25(+)CD4(+) regulatory T cells (T4reg) might hamper effective immunosurveillance of emerging cancer cells and impede effective immune responses to established tumours. In this descriptive study, we analysed blood and tissue regulatory T cell populations in patients with CRC. METHODS: Blood and tissue regulatory Foxp3(+) T cells from 40 patients with CRC were compared to regulatory Foxp3(+) T cells from normal colonic tissue and from blood of 26 healthy volunteers. Flow cytometry was used to quantify and phenotype all Foxp3(+) T cell populations. Correlations were sought with the tumour stage and with micro-invasive status. The suppressive capacity of regulatory Foxp3(+) T cells was assessed by their effect on CD4(+)CD25(-) T cell proliferation in vitro and by their capacity to inhibit cytokine production by conventional T cells. RESULTS: We found a significant increase of CD8(+)CD25(+)Foxp3(+) cells (T8reg) in blood and CRC tissue; their phenotype was close to that of T4reg. T8reg cells infiltrating CRC were activated, as suggested by increased cytoxic T lymphocyte-associated antigen-4, glucocorticoid-induced tumour necrosis factor-related protein, and transforming growth factor (TGF)beta1 expression compared to T8reg from normal autologous colonic tissue. Moreover, T8reg were able to suppress CD4(+)CD25(-) T cell proliferation and Th1 cytokine production ex vivo, demonstrating that tumour-infiltrating T8reg have strong suppressive capacities. T8reg numbers correlated with the tumour stage and with micro-invasive status. Finally, interleukin 6 and TGF beta 1 synergistically induced the generation of CD8(+)CD25(+)Foxp3(+) T cells ex vivo. CONCLUSIONS: We have identified a new regulatory T cell population (CD8(+)Foxp3(+)) in colorectal tumours. After isolation from cancer tissue these CD8(+)Foxp3(+) cells demonstrated strong immunosuppressive properties in vitro. These data suggest that these cells may contribute to tumoral immune escape and disease progression.
- Subjects :
- CD4-Positive T-Lymphocytes
Male
MESH: Neoplasm Proteins
MESH: T-Lymphocyte Subsets
Lymphocyte Activation
T-Lymphocytes, Regulatory
Interleukin 21
0302 clinical medicine
MESH: Aged, 80 and over
T-Lymphocyte Subsets
Cytotoxic T cell
Medicine
IL-2 receptor
MESH: Lymphocytes, Tumor-Infiltrating
Aged, 80 and over
MESH: Aged
MESH: Cytokines
MESH: Middle Aged
Gastroenterology
FOXP3
MESH: CD4-Positive T-Lymphocytes
Forkhead Transcription Factors
MESH: Neoplasm Staging
Middle Aged
Neoplasm Proteins
3. Good health
medicine.anatomical_structure
030220 oncology & carcinogenesis
Cytokines
Female
Colorectal Neoplasms
Adult
MESH: Immune Tolerance
MESH: Lymphocyte Count
MESH: Immunophenotyping
Regulatory T cell
T cell
chemical and pharmacologic phenomena
Adenocarcinoma
Immunophenotyping
03 medical and health sciences
Lymphocytes, Tumor-Infiltrating
MESH: Forkhead Transcription Factors
MESH: Cell Proliferation
Immune Tolerance
Humans
Neoplasm Invasiveness
Lymphocyte Count
MESH: Lymphocyte Activation
Aged
Cell Proliferation
Neoplasm Staging
MESH: Humans
business.industry
MESH: T-Lymphocytes, Regulatory
MESH: Adenocarcinoma
MESH: Adult
MESH: Neoplasm Invasiveness
[SDV.IMM.IMM]Life Sciences [q-bio]/Immunology/Immunotherapy
MESH: Male
Cancer cell
Immunology
business
MESH: Female
CD8
MESH: Colorectal Neoplasms
030215 immunology
Subjects
Details
- Language :
- English
- ISSN :
- 00175749 and 14683288
- Database :
- OpenAIRE
- Journal :
- Gut, Gut, BMJ Publishing Group, 2009, 58 (4), pp.520-9. ⟨10.1136/gut.2008.158824⟩, Gut, 2009, 58 (4), pp.520-9. ⟨10.1136/gut.2008.158824⟩
- Accession number :
- edsair.doi.dedup.....36caf85eaa557f7eb50834db208f1223