CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题：Cyclophosphamide depletes tumor infiltrating T regulatory cells and combined with anti-PD-1 therapy improves survival in murine neuroblastoma.
Cyclophosphamide depletes tumor infiltrating T regulatory cells and combined with anti-PD-1 therapy improves survival in murine neuroblastoma.
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尽管采用了强化的多模式治疗方案，高危神经母细胞瘤患儿的预后仍然很差。当前治疗的毒性显著，需要新的方法来改善预后。环磷酰胺（CPM）是当前化疗方案的关键组成部分，已知具有免疫调节作用。然而，这一点尚未在神经母细胞瘤TIL（肿瘤浸润淋巴细胞）的背景下进行研究。利用神经母细胞瘤小鼠模型，通过详细的免疫表型分析研究了低剂量CPM的免疫调节作用。我们证明CPM通过凋亡导致瘤内T调节细胞的特异性耗竭，当与抗PD-1抗体治疗联合时，可改善治疗效果。CPM联合抗PD-1治疗被证明是一种有效的联合治疗，在更具耐药性的肿瘤模型中，节拍式CPM比单次给药更有效。总体而言，这些临床前数据强烈支持在神经母细胞瘤中对这类联合策略进行临床评估。
The outcome for children with high-risk neuroblastoma is poor despite intensive multi-modal treatment protocols. Toxicity from current treatments is significant, and novel approaches are needed to improve outcome. Cyclophosphamide (CPM) is a key component of current chemotherapy regimens and is known to have immunomodulatory effects.
However, this has not been investigated in the context of tumor infiltrating lymphocytes in neuroblastoma. Using murine models of neuroblastoma, the immunomodulatory effects of low-dose CPM were investigated using detailed immunophenotyping.
We demonstrated that CPM resulted in a specific depletion of intratumoral T regulatory cells by apoptosis, and when combined with anti-PD-1 antibody therapy, this resulted in improved therapeutic efficacy. CPM combined with anti-PD-1 therapy was demonstrated to be an effective combinational therapy, with metronomic CPM found to be more effective than single dosing in more resistant tumor models.
Overall, this pre-clinical data strongly support clinical evaluation of such combination strategies in neuroblastoma.
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