反映人类疾病的小鼠模型是将基础科学发现转化为临床疗法的无价工具。然而，这些体内治疗研究中许多是短期的并且不能准确地模拟患者情况。在本研究中，我们利用完全免疫能力的转基因小鼠模型TGS，其中转基因引起黑色素瘤转移的是正常神经元受体谷氨酸代谢型受体1（mGluR1）的异位表达，以评估长期（长达8个月）使用谷氨酸能信号抑制剂troriluzole（riluzole的前药）和程序性细胞死亡蛋白-1（PD-1）抗体作为治疗反应的模型。我们的结果显示，在troriluzole和/或抗PD-1治疗的雄性小鼠中，治疗反应存在性别差异，与肿瘤基质界面中差异性CD8+ T细胞和CD11b+髓样细胞群体相符，支持这种模型是一个反应灵敏且可控的系统，可用于评估免疫能力环境中的黑色素瘤治疗方案。版权所有©2023 The Authors，Elsevier Inc.所有权利保留。

Mouse models that reflect human disorders provide invaluable tools towards the translation of basic science discoveries to clinical therapies. However, many of these in vivo therapeutic studies are short-term and do not accurately mimic patient conditions. In this study, we utilized a fully immuno-competent, transgenic mouse model, TGS, in which the spontaneous development of metastatic melanoma is driven by the ectopic expression of a normal neuronal receptor, metabotropic glutamate receptor 1 (mGluR1), as a model to assess longitudinal treatment response (up to 8 months) with an inhibitor of glutamatergic signaling, troriluzole, a prodrug of riluzole, plus an antibody against programmed cell death protein-1 (PD-1), an immune-checkpoint inhibitor. Our results reveal a sex-biased treatment response that led to an improved survival in troriluzole and/or anti-PD-1 treated male mice that correlated with differential CD8+ T-cells and CD11b+ myeloid cell populations in the tumor-stromal interface, supporting the notion that this model is a responsive and tractable system for evaluating therapeutic regimens for melanoma in an immuno-competent setting.Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.