Very low mutation burden is a feature of inflamed recurrent glioblastomas responsive to cancer immunotherapy.
Very low mutation burden is a feature of inflamed recurrent glioblastomas responsive to cancer immunotherapy.
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非常低的突变负担是反应癌症免疫疗法的反复发生的胶质母细胞瘤的特征。
DOI：
10.1038/s41467-020-20469-6
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发表时间：
2021-01-13
影响因子：
16.6
通讯作者：
Ashley DM
中科院分区：
文献类型：
--
作者：
Gromeier M;Brown MC;Zhang G;Lin X;Chen Y;Wei Z;Beaubier N;Yan H;He Y;Desjardins A;Herndon JE 2nd;Varn FS;Verhaak RG;Zhao J;Bolognesi DP;Friedman AH;Friedman HS;McSherry F;Muscat AM;Lipp ES;Nair SK;Khasraw M;Peters KB;Randazzo D;Sampson JH;McLendon RE;Bigner DD;Ashley DM
复发性胶质母细胞瘤的几项免疫治疗临床试验报告了10-20%患者的长期生存益处。在这里，我们对免疫治疗干预前获得的复发性WHO IV级胶质母细胞瘤患者的肿瘤组织进行基因组分析。我们报告，非常低的肿瘤突变负荷与重组脊髓灰质炎病毒治疗或免疫检查点阻断后复发性胶质母细胞瘤患者的生存期延长相关。在免疫治疗初治的新诊断或复发性胶质母细胞瘤患者队列中未观察到肿瘤突变负荷与生存期之间的关系。转录组学分析揭示了肿瘤突变负荷和炎症基因特征在复发性但不是新诊断的胶质母细胞瘤肿瘤的队列中的富集之间的反比关系，这意味着肿瘤突变负荷和肿瘤内在炎症之间的关系在复发后演变。复发性胶质母细胞瘤（rGBM）的结局令人沮丧，但在免疫治疗后的患者亚群中观察到了长期生存。在这里，作者报告了rGBM患者免疫治疗后低肿瘤突变负荷、炎症基因特征和生存率之间的正相关性。
Several immunotherapy clinical trials in recurrent glioblastoma have reported long-term survival benefits in 10–20% of patients. Here we perform genomic analysis of tumor tissue from recurrent WHO grade IV glioblastoma patients acquired prior to immunotherapy intervention. We report that very low tumor mutation burden is associated with longer survival after recombinant polio virotherapy or after immune checkpoint blockade in recurrent glioblastoma patients. A relationship between tumor mutation burden and survival is not observed in cohorts of immunotherapy naïve newly diagnosed or recurrent glioblastoma patients. Transcriptomic analyses reveal an inverse relationship between tumor mutation burden and enrichment of inflammatory gene signatures in cohorts of recurrent, but not newly diagnosed glioblastoma tumors, implying that a relationship between tumor mutation burden and tumor-intrinsic inflammation evolves upon recurrence. Recurrent glioblastomas (rGBM) have dismal outcomes, but long-term survival has been observed in subsets of patients after immunotherapy. Here the authors report a positive association between low tumor mutation burden, inflammatory gene signatures, and survival after immunotherapy in rGBM patients.
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影响因子：
--
作者：
Filley AC;Henriquez M;Dey M
通讯作者：
Dey M
影响因子：
7.3
作者：
Gao J;Aksoy BA;Dogrusoz U;Dresdner G;Gross B;Sumer SO;Sun Y;Jacobsen A;Sinha R;Larsson E;Cerami E;Sander C;Schultz N
通讯作者：
Schultz N
影响因子：
17.1
作者：
Brown MC;Holl EK;Boczkowski D;Dobrikova E;Mosaheb M;Chandramohan V;Bigner DD;Gromeier M;Nair SK
通讯作者：
Nair SK
影响因子：
17.1
作者：
Subudhi, Sumit K.;Vence, Luis;Sharma, Padmanee
通讯作者：
Sharma, Padmanee
影响因子：
45.3
作者：
Lang, Frederick F.;Conrad, Charles;Fueyo, Juan
通讯作者：
Fueyo, Juan