Br J Cancer:免疫检查点阻断治疗诱导的自身免疫与转移性黑色素瘤的预后和独特的T细胞表达谱相关

2021-03-23 xiaozeng MedSci原创

免疫检查点阻断(ICB)疗法是一类通过介导T细胞活性来提高抗肿瘤免疫反应的治疗方法。

免疫检查点阻断(ICB)疗法是一类通过介导T细胞活性来提高抗肿瘤免疫反应的治疗方法。目前已应用于转移性黑色素瘤(MM)的治疗中。当前的ICB标准治疗策略包括抗PD1单药治疗(nivolumab或pembrolizumab,sICB)或抗CTLA-4/抗PD1(ipilimumab和nivolumab,cICB)联合治疗。

ICB能够激活CD8+T细胞,进而引起抗性的产生和免疫相关不良反应(irAEs)的发生。然而,irAEs与基线参数以及临床结果之间的关系尚不清楚。

该研究旨在对接受单药治疗或联合治疗的转移性黑色素瘤患者的原发(N=144)和继发(N=211)独立队列中irAEs与患者的生存进行回顾性评估。对来自治疗前和治疗后CD8+T细胞的RNA进行测序,并根据irAE情况评估差异基因的表达。

患者总生存期(OS)和无进展生存期(PFS)的Kaplan-Meier曲线分析

结果显示,58.3%的患者出现早期irAE,这与两个队列中较长的无进展(PFS)和总体生存期(OS)相关。没有发生irAEs的患者的中位生存期为16.6个月。

CD8+T细胞中不同基因的表达情况

治疗前单核细胞和中性粒细胞数量而非BMI值是患者临床结局的补充预测指标。根据irAE的发生情况,研究人员在CD8+T细胞中观察到了许多基因通路成员的差异表达,无irAE发生的患者中则发现,在治疗前后CXCR1的表达水平均上调。


总而言之,该研究结果显示,在ICB治疗后irAE的早期发生与MM患者的较好生存状况相关。 irAEs的发生与诸多基因通路的表达相关,这表明irAE能够部分反映基线免疫作用的激活。


原始出处:

Ye, W., Olsson-Brown, A., Watson, R.A. et al. Checkpoint-blocker-induced autoimmunity is associated with favourable outcome in metastatic melanoma and distinct T-cell expression profiles. Br J Cancer (15 March 2021).

 

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    2021-07-07 sunylz
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最近对儿童的自然史研究表明,特定的HLA基因型与免疫反应的第一个抗原靶点之间存在联系。然而目前,关于特异性HLA分子对1型糖尿病等自身免疫性疾病病理影响的分子基础尚不清楚。本研究以一种常见的糖尿病相关HLA单倍型为背景,通过探讨胰岛抗原的致糖尿病性来研究这种体内联系。

Neurology病例:自身免疫性胶质纤维酸性蛋白脑膜脑脊髓炎

73岁骨髓增生异常综合征女性,表现为认知和运动能力下降2月,伴有头痛和体重下降。查体提示患者思睡,对称齿轮样肌强直,运动迟缓,上臂肌阵挛和反射亢进。

Nat Commun:自身免疫性肺泡蛋白沉积症发病风险相关遗传决定因素

肺泡蛋白沉积症(PAP)是一种罕见的弥漫性肺部疾病,在全球中每百万人有6-7例患病。

Arthritis Rheumatol:美国人群中抗核抗体的患病率升高

近年来,美国ANA的患病率明显升高。