J Immunother Cancer：肥胖会减弱肾癌患者采用抗PD-1免疫治疗的疗效

2021-01-13 MedSci原创 MedSci原创

肥胖是肾癌的一个主要危险因素，但我们对其对抗肿瘤免疫和免疫治疗结果的影响仍不完全了解。考虑到越来越多的免疫检查点抑制剂将用于治疗转移性疾病，以及越来越多的证据表明，在癌症免疫疗法的背景下存在肥胖悖论

肥胖是肾癌的一个主要危险因素，但我们对其对抗肿瘤免疫和免疫治疗结果的影响仍不完全了解。考虑到越来越多的免疫检查点抑制剂将用于治疗转移性疾病，以及越来越多的证据表明，在癌症免疫疗法的背景下存在肥胖悖论（肥胖癌症患者预后相对较好），因此破译这些关联至关重要。

本研究在肾细胞癌(RCC)患者和肾肿瘤小鼠模型中研究了宿主肥胖和以抗程序性细胞死亡蛋白(PD-1)为基础的治疗的预后之间的关系。对73位接受标准抗PD-1治疗的晚期肾癌患者进行了6个多月的随访，计算了总生存期(OS)和无进展生存期(PFS)。此外，研究人员还收集19位初治肾肿瘤患者的肿瘤组织，按体重指数(BMI)分为肥胖(BMI≥30 kg/m)和非肥胖(BMI<30 kg/m)两组，采用流式细胞仪检测肿瘤组织内CD8+ T细胞的比例和表型，包括PD-1状态。予以小鼠联合抗PD-1治疗，评估抗肿瘤免疫。

肥胖与激活的初治患者PD-1hiCD8+ TILs频率降低有关

在肥胖患者中，接受抗PD-1治疗的肾癌患者表现出较短的PFS(p=0.0448)和OS(p=0.0288)。初治肾癌患者肿瘤组织中的浸润性PD-1^high CD8+ T细胞的频率降低，该结果在小鼠模型中得到了验证。

不同处理方式的肾肿瘤小鼠的存活率

经抗PD-1免疫治疗后，瘦小鼠和肥胖小鼠都有不同的治疗反应者和无反应者；然而，肥胖降低了治疗反应者的比例(73%瘦小鼠 vs 44%肥胖小鼠)。瘦的和肥胖的对治疗有应答的小鼠的肿瘤表现出相似的免疫遗传学特征，主要是PD-1^int干扰素（IFN）γ⁺CD8⁺ T细胞浸润，髓系来源的抑制细胞（MDSC）减少，获得了较有利的CD44⁺CD8⁺ T细胞和MDSC的比率。中和肥胖小鼠的白细胞介素(IL)-1β可将治疗应答率提高到58%，并减少肿瘤中MDS的积聚。

综上，该研究表明，肥胖与肾癌抗PD-1治疗的疗效降低有关，部分原因是炎症性IL-1β水平升高，强调了对这一关键问题继续研究的必要性。

原始出处：

Shannon K Boi, et al. Obesity diminishes response to PD-1-based immunotherapies in renal cancer. Journal for ImmunoTherapy of Cancer. 2020;8:e000725. doi:10.1136/jitc-2020-000725

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2021-01-15 dinorsor524

#PD-1免疫治疗#

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2021-01-14 内科新手

谢谢梅斯提供这么好的信息，学到很多

99 0
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2021-01-14 智者为医08

#抗PD-1免疫治疗#

134 0
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2021-01-14 zb1235672

#肾癌#

269 0
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2021-01-13 Nebula-Qin

#肾癌##肥胖#

263 0
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2021-01-13 Mayyyyy

学习

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J Immunother Cancer：肥胖会减弱肾癌患者采用抗PD-1免疫治疗的疗效

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