Hospicells derived from ovarian cancer stroma inhibit T-cell immune responses

Ludovic Martinet, Rémy Poupot, Pejman Mirshahi, Arash Rafii Tabrizi, Jean Jacques Fournié, Massoud Mirshahi, Mary Poupot

Research output: Contribution to journalArticle

26 Citations (Scopus)

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 languageEnglish
Pages (from-to)2143-2152
Number of pages10
JournalInternational Journal of Cancer
Volume126
Issue number9
DOIs
Publication statusPublished - 1 May 2010
Externally publishedYes

Fingerprint

Ovarian Neoplasms
T-Lymphocytes
Tumor Microenvironment
Carcinoma
Immunosuppression
Neoplasms
Indoleamine-Pyrrole 2,3,-Dioxygenase
Nitric Oxide Synthase Type II
Stromal Cells
Tryptophan
Immunity
Nitric Oxide
Cytokines
Neoplasm Metastasis
Drug Therapy

Keywords

  • Immune regulation
  • Ovarian carcinoma
  • T cells
  • Tumor microenvironment

ASJC Scopus subject areas

  • Medicine(all)
  • Oncology
  • Cancer Research

Cite this

Martinet, L., Poupot, R., Mirshahi, P., Tabrizi, A. R., Fournié, J. J., Mirshahi, M., & Poupot, M. (2010). Hospicells derived from ovarian cancer stroma inhibit T-cell immune responses. International Journal of Cancer, 126(9), 2143-2152. https://doi.org/10.1002/ijc.24881

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 journalArticle

Martinet, L, Poupot, R, Mirshahi, P, Tabrizi, AR, Fournié, JJ, Mirshahi, M & Poupot, M 2010, 'Hospicells derived from ovarian cancer stroma inhibit T-cell immune responses', International Journal of Cancer, vol. 126, no. 9, pp. 2143-2152. https://doi.org/10.1002/ijc.24881
Martinet, Ludovic ; Poupot, Rémy ; Mirshahi, Pejman ; Tabrizi, Arash Rafii ; Fournié, Jean Jacques ; Mirshahi, Massoud ; Poupot, Mary. / Hospicells derived from ovarian cancer stroma inhibit T-cell immune responses. In: International Journal of Cancer. 2010 ; Vol. 126, No. 9. pp. 2143-2152.
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