A Quantitative Deficiency in Peripheral Blood V gamma 9V delta 2 Cells Is a Negative Prognostic Biomarker in Ovarian Cancer Patients

作者：Thedrez Aurelie^*; Lavoue Vincent; Dessarthe Benoit; Daniel Pascale; Henno Sebastien; Jaffre Isabelle; Leveque Jean; Catros Veronique; Cabillic Florian

来源：PLos One, 2013, 8(5): e63322.

DOI：10.1371/journal.pone.0063322

V gamma 9V delta 2 cells are cytotoxic T cells that are able to recognize epithelial ovarian carcinoma (EOC) cells. Therefore, V gamma 9V delta 2 cell-based adoptive transfer is an attractive therapy for EOC. However, the inefficient ex vivo expansion after specific stimulation of V gamma 9V delta 2 cells from some patients and the relationships between V gamma 9V delta 2 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 V gamma 9V delta 2 cells. The compounds differed in their efficacies to induce ex vivo V gamma 9V delta 2 PBMC expansion, but 16/60 samples remained inefficiently expanded with both stimuli. Interestingly, the V gamma 9V delta 2 cells in these low-responding PBMCs displayed before expansion (ex vivo PBMCs) an altered production of the pro-inflammatory cytokines IFN-gamma and TNF-alpha, a decreased naive fraction and a reduced frequency. No evidence of an involvement of CD4(+)CD25(+)Foxp(3+) regulatory cells was observed. Importantly, our data also demonstrate that a V gamma 9V delta 2 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 V gamma 9V delta 2 cells to the anti-tumor effects of chemotherapeutic agents and they strengthen interest in strategies that might increase V gamma 9V delta 2 cells in cancer patients.

• 出版日期2013-5-23