Abstract
With metastatic disease at diagnosis for 70% of patients, ovarian cancer represents the most lethal gynecological malignancy. Ovarian carcinomas are aggressive malignancies that can evade immune surveillance and frequently develop into metastases. The tumor microenvironment is decisive for preventing immune attack but, in the case of ovarian carcinoma, the mechanisms are unclear. We recently isolated a novel type of stromal cell from the ascitis of patients with ovarian carcinoma that interacts with epithelial ovarian cancers conferring them chemoresistance. These cells, called Hospicells, have the cell surface markers CD9, CD10, CD29, CD146 and CD166. Here, we investigated whether Hospicells also have immunomodulatory functions that might interfere with immunity to cancer. We report that Hospicells inhibit the proliferation of human CD4+, CD8+ and Vγ9Vδ2 T cells in vitro and the production of cytokines by these immune cells. The immunosuppression of CD4+ T cells is independent of direct contact with the Hospicells and is mainly due to nitric oxide produced by the inducible nitric oxide synthase and to products of the tryptophan degradation by indoleamine 2,3-dioxygenase. We proposed that Hospicells in the microenvironment of the tumor mediate immunosuppression of T cells and thus allow ovarian cancers to evade immune surveillance. Targeting of Hospicells could be an alternative to strong chemotherapy through the recovery of immune responses against tumor cells.
| Original language | English |
|---|---|
| Pages (from-to) | 2143-2152 |
| Number of pages | 10 |
| Journal | International Journal of Cancer |
| Volume | 126 |
| Issue number | 9 |
| DOIs | |
| Publication status | Published - 1 May 2010 |
| Externally published | Yes |
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Keywords
- Immune regulation
- Ovarian carcinoma
- T cells
- Tumor microenvironment
ASJC Scopus subject areas
- Medicine(all)
- Oncology
- Cancer Research
Cite this
Hospicells derived from ovarian cancer stroma inhibit T-cell immune responses. / Martinet, Ludovic; Poupot, Rémy; Mirshahi, Pejman; Tabrizi, Arash Rafii; Fournié, Jean Jacques; Mirshahi, Massoud; Poupot, Mary.
In: International Journal of Cancer, Vol. 126, No. 9, 01.05.2010, p. 2143-2152.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Hospicells derived from ovarian cancer stroma inhibit T-cell immune responses
AU - Martinet, Ludovic
AU - Poupot, Rémy
AU - Mirshahi, Pejman
AU - Tabrizi, Arash Rafii
AU - Fournié, Jean Jacques
AU - Mirshahi, Massoud
AU - Poupot, Mary
PY - 2010/5/1
Y1 - 2010/5/1
N2 - With metastatic disease at diagnosis for 70% of patients, ovarian cancer represents the most lethal gynecological malignancy. Ovarian carcinomas are aggressive malignancies that can evade immune surveillance and frequently develop into metastases. The tumor microenvironment is decisive for preventing immune attack but, in the case of ovarian carcinoma, the mechanisms are unclear. We recently isolated a novel type of stromal cell from the ascitis of patients with ovarian carcinoma that interacts with epithelial ovarian cancers conferring them chemoresistance. These cells, called Hospicells, have the cell surface markers CD9, CD10, CD29, CD146 and CD166. Here, we investigated whether Hospicells also have immunomodulatory functions that might interfere with immunity to cancer. We report that Hospicells inhibit the proliferation of human CD4+, CD8+ and Vγ9Vδ2 T cells in vitro and the production of cytokines by these immune cells. The immunosuppression of CD4+ T cells is independent of direct contact with the Hospicells and is mainly due to nitric oxide produced by the inducible nitric oxide synthase and to products of the tryptophan degradation by indoleamine 2,3-dioxygenase. We proposed that Hospicells in the microenvironment of the tumor mediate immunosuppression of T cells and thus allow ovarian cancers to evade immune surveillance. Targeting of Hospicells could be an alternative to strong chemotherapy through the recovery of immune responses against tumor cells.
AB - With metastatic disease at diagnosis for 70% of patients, ovarian cancer represents the most lethal gynecological malignancy. Ovarian carcinomas are aggressive malignancies that can evade immune surveillance and frequently develop into metastases. The tumor microenvironment is decisive for preventing immune attack but, in the case of ovarian carcinoma, the mechanisms are unclear. We recently isolated a novel type of stromal cell from the ascitis of patients with ovarian carcinoma that interacts with epithelial ovarian cancers conferring them chemoresistance. These cells, called Hospicells, have the cell surface markers CD9, CD10, CD29, CD146 and CD166. Here, we investigated whether Hospicells also have immunomodulatory functions that might interfere with immunity to cancer. We report that Hospicells inhibit the proliferation of human CD4+, CD8+ and Vγ9Vδ2 T cells in vitro and the production of cytokines by these immune cells. The immunosuppression of CD4+ T cells is independent of direct contact with the Hospicells and is mainly due to nitric oxide produced by the inducible nitric oxide synthase and to products of the tryptophan degradation by indoleamine 2,3-dioxygenase. We proposed that Hospicells in the microenvironment of the tumor mediate immunosuppression of T cells and thus allow ovarian cancers to evade immune surveillance. Targeting of Hospicells could be an alternative to strong chemotherapy through the recovery of immune responses against tumor cells.
KW - Immune regulation
KW - Ovarian carcinoma
KW - T cells
KW - Tumor microenvironment
UR - http://www.scopus.com/inward/record.url?scp=77949889992&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=77949889992&partnerID=8YFLogxK
U2 - 10.1002/ijc.24881
DO - 10.1002/ijc.24881
M3 - Article
C2 - 19739080
AN - SCOPUS:77949889992
VL - 126
SP - 2143
EP - 2152
JO - International Journal of Cancer
JF - International Journal of Cancer
SN - 0020-7136
IS - 9
ER -