A quantitative deficiency in peripheral blood Vγ9Vδ2 cells is a negative prognostic biomarker in ovarian cancer patients.Reportar como inadecuado

A quantitative deficiency in peripheral blood Vγ9Vδ2 cells is a negative prognostic biomarker in ovarian cancer patients. - Descarga este documento en PDF. Documentación en PDF para descargar gratis. Disponible también para leer online.

* Corresponding author 1 Foie, métabolismes et cancer 2 Service de Gynécologie et Obstétrique Rennes 3 Service de Cytogénétique et de Biologie Cellulaire 4 Service d-anatomie et cytologie pathologiques Rennes 5 ICO Nantes - Institut de cancérologie de l-Ouest - Nantes

Abstract : Vγ9Vδ2 cells are cytotoxic T cells that are able to recognize epithelial ovarian carcinoma EOC cells. Therefore, Vγ9Vδ2 cell-based adoptive transfer is an attractive therapy for EOC. However, the inefficient ex vivo expansion after specific stimulation of Vγ9Vδ2 cells from some patients and the relationships between Vγ9Vδ2 cells and clinical course of EOC are issues that remain to be clarified. Herein, peripheral blood mononuclear cells PBMCs from 60 EOC patients were stimulated with bromohydrin pyrophosphate BrHPP or zoledronate, which are specific agonists of Vγ9Vδ2 cells. The compounds differed in their efficacies to induce ex vivo Vγ9Vδ2 PBMC expansion, but 16-60 samples remained inefficiently expanded with both stimuli. Interestingly, the Vγ9Vδ2 cells in these low-responding PBMCs displayed before expansion ex vivo PBMCs an altered production of the pro-inflammatory cytokines IFN-γ and TNF-α, a decreased naive fraction and a reduced frequency. No evidence of an involvement of CD4+CD25+Foxp3+ regulatory cells was observed. Importantly, our data also demonstrate that a Vγ9Vδ2 cell frequency of 0.35% or less in EOC PBMCs could be used to predict low responses to both BrHPP and zoledronate. Moreover, our data highlight that such a deficiency is not correlated with advanced EOC stages but is associated with more refractory states to platinum-based chemotherapy and is an independent predictor of shorter disease-free survival after treatment. These results are the first to suggest a potential contribution of Vγ9Vδ2 cells to the anti-tumor effects of chemotherapeutic agents and they strengthen interest in strategies that might increase Vγ9Vδ2 cells in cancer patients.

Autor: Aurélie Thedrez - Vincent Lavoué - Benoit Dessarthe - Pascale Daniel - Sébastien Henno - Isabelle Jaffre - Jean Levêque - Vé

Fuente: https://hal.archives-ouvertes.fr/


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