Hospicells derived from ovarian cancer stroma inhibit T-cell immune responses.
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 Vgamma9Vdelta2 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.
Martinet
Ludovic
L
INSERM, U563, Centre de Physiopathologie de Toulouse-Purpan and Université Paul-Sabatier, Toulouse, France.
Poupot
Rémy
R
Mirshahi
Pejman
P
Rafii
Arash
A
Fournié
Jean-Jacques
JJ
Mirshahi
Massoud
M
Poupot
Mary
M
D002450:Cell Communication; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis; D005260:Female; D006801:Humans; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase / Q000502:physiology; D008213:Lymphocyte Activation; D052247:Nitric Oxide Synthase Type II / Q000502:physiology; D010051:Ovarian Neoplasms / Q000276:immunology* / Q000473:pathology*; D011948:Receptors, Antigen, T-Cell / Q000502:physiology; D017154:Stromal Cells / Q000502:physiology*; D013601:T-Lymphocytes / Q000276:immunology*
D016207:Cytokines; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D011948:Receptors, Antigen, T-Cell; D052247:Nitric Oxide Synthase Type II