Service d'Immunologie Biologique Hôpital Européen Georges Pompidou (HEGP), AP-HP, Paris, France.
J Immunother. 2010 Nov-Dec;33(9):991-8. doi: 10.1097/CJI.0b013e3181f4c208.
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 response. Antiangiogenic therapy also reversed immunosuppression in the tumor microenvironment which provides novel argument in human to favor its combination with immunotherapy.
舒尼替尼是一种抗血管生成分子，是转移性肾细胞癌治疗的一线标准治疗方法之一。然而，它仅对一部分患者有效，目前尚未确定舒尼替尼疗效的预测标志物。28 例转移性肾细胞癌患者接受了舒尼替尼为基础的治疗，另有 7 例原发性肾细胞癌患者在新辅助试验中也接受了舒尼替尼治疗。在一项前瞻性研究中，我们在每个治疗周期前后测量了血液和肿瘤中 CD3+CD4+CD25(hi)Foxp3+调节性 T 细胞（一种免疫抑制细胞群）的数量。我们观察到，在接受舒尼替尼为基础的治疗后，每个周期外周血 Foxp3+调节性 T 细胞的数量减少。在接受 2 或 3 个周期治疗后，Foxp3+调节性 T 细胞数量减少的患者总生存率显著延长（P<0.05）。调节性 T 细胞数量的减少与治疗前的数量呈正相关（P<0.01），但与实体瘤反应评价标准定义的肿瘤体积的改变无关。在新辅助试验中接受舒尼替尼治疗的 7 例患者中有 5 例肿瘤内调节性 T 细胞减少，这也支持了这些结果的临床相关性。我们的研究是首次报道调节性 T 细胞的测量可能对抗血管生成反应具有预测价值的工作。抗血管生成治疗还逆转了肿瘤微环境中的免疫抑制，这为在人类中支持其与免疫治疗联合提供了新的论据。
