A Decrease of Regulatory T Cells Correlates With Overall Survival After Sunitinib-based Antiangiogenic Therapy in Metastatic Renal Cancer Patients

作者：Olivier Adotévi, Hélène Péré, Patrice Ravel, Nacilla Haicheur, Cécile Badoual, Nathalie Merillon, Jacques Médioni, Séverine Peyrard, Stéphane Roncelin, Virginie Verkarre, Arnaud Méjean, Wolf H. Fridman, Stéphane Oudard, Éric Tartour · 发表于：Journal of Immunotherapy · 年份：2010 · DOI：10.1097/cji.0b013e3181f4c208 · 被引用次数：209 · 研究领域：Cancer Immunotherapy and Biomarkers、CAR-T cell therapy research、Renal cell carcinoma treatment

Sunitinib, an antiangiogenic molecule, is one of the first-line standard of care in the treatment of patients with metastatic renal cell carcinoma. However, it only benefits to a subgroup of patients and no predictive markers of sunitinib efficacy have been identified. Twenty-eight metastatic renal cell carcinomas were treated with sunitinib-based therapy and another subgroup of 7 primary renal cell cancer patients were also treated by sunitinib in a neoadjuvant trial. Measurements of CD3+CD4+CD25(hi) Foxp3+ regulatory T cells, an immunosuppressive cell population, were performed before and after each cycle of treatment in blood and tumor in a prospective study. We observed a decrease in the number of peripheral blood Foxp3+ regulatory T cells after each cycle of sunitinib-based therapy. The overall survival was significantly longer in patients showing a decrease in the number of Foxp3+ regulatory T cells after 2 or 3 cycles of treatment (P<0.05). The decrease in the number of regulatory T cells positively correlated with their number at baseline (P<0.01), but not with modification of tumor volume defined by Response Evaluation Criteria in Solid Tumors criteria. The clinical relevance of these results was also supported by an intratumoral decrease of regulatory T cells in 5 out of 7 patients treated by sunitinib in a neoadjuvant trial. Our study represents the first work reporting that the measurement of regulatory T cells may have a predictive value on antiangiogenic respons...