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ERK1/2磷酸化预测复发性胶质母细胞瘤抗pd -1免疫治疗后的生存率

原文发布日期：2021-11-29

英文摘要：

摘要翻译：

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文章：

ERK1/2磷酸化预测复发性胶质母细胞瘤抗pd -1免疫治疗后的生存率

ERK1/2 phosphorylation predicts survival following anti-PD-1 immunotherapy in recurrent glioblastoma

原文发布日期：2021-11-29

英文摘要：

Only a subset of recurrent glioblastoma (rGBM) responds to anti-PD-1 immunotherapy. Previously, we reported enrichment of BRAF/PTPN11 mutations in 30% of rGBM that responded to PD-1 blockade. Given that BRAF and PTPN11 promote MAPK/ERK signaling, we investigated whether activation of this pathway is associated with response to PD-1 inhibitors in rGBM, including patients that do not harbor BRAF/PTPN11 mutations. Here we show that immunohistochemistry for ERK1/2 phosphorylation (p-ERK), a marker of MAPK/ERK pathway activation, is predictive of overall survival following adjuvant PD-1 blockade in two independent rGBM patient cohorts. Single-cell RNA-sequencing and multiplex immunofluorescence analyses revealed that p-ERK was mainly localized in tumor cells and that high-p-ERK GBMs contained tumor-infiltrating myeloid cells and microglia with elevated expression of MHC class II and associated genes. These findings indicate that ERK1/2 activation in rGBM is predictive of response to PD-1 blockade and is associated with a distinct myeloid cell phenotype.

摘要翻译：

仅有一部分复发性胶质母细胞瘤（rGBM）对抗PD-1免疫治疗有效。此前，我们报道，在接受PD-1阻滞剂治疗 responders中，BRAF/PTPN11突变的患者占30%。由于BRAF和PTPN11促进MAPK/ERK信号通路激活，我们探讨了ERK信号通路激活与rGBM PD-1抑制剂治疗效果之间的关联，包括无BRAF/PTPN11突变患者。本研究显示，在辅助PD-1阻断后，对rGBM患者的ERK1/2磷酸化（p-ERK）免疫组织化学标记预测后续总生存期，在两个独立的rGBM患者队列中具有显著预测性。通过单细胞RNA测序和多重免疫荧光分析发现，p-ERK主要位于肿瘤细胞中，并且高p-ERK GBMs包含肿瘤浸润性 myeloid 细胞和微胶质细胞，这些细胞富含MHC类II及其相关基因的表达。这些发现表明，在rGBM中，ERK1/2激活是预测PD-1阻断治疗反应的一个因素，并与一种特定的 myeloid 细胞亚型相关联。