Immunogenomic Landscape Contributes to Hyperprogressive Disease after Anti-PD-1 Immunotherapy for Cancer.
Immunogenomic Landscape Contributes to Hyperprogressive Disease after Anti-PD-1 Immunotherapy for Cancer.
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DOI：
10.1016/j.isci.2018.10.021
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发表时间：
2018-11-30
期刊：
影响因子：
5.8
通讯作者：
You M
中科院分区：
文献类型：
--
作者：
Xiong D;Wang Y;Singavi AK;Mackinnon AC;George B;You M
尽管 PD-1 阻断免疫疗法显示出显着的治疗前景，但部分患者在抗 PD-1 免疫疗法后可能会出现过度进展性疾病 (HPD)，肿瘤生长加速。为了阐明其潜在机制，我们比较了两名在抗 PD-1 免疫治疗后发生 HPD 的患者治疗前和治疗后肿瘤之间的突变和转录情况。在治疗后的 HPD 肿瘤中，在已知的癌症基因中发现了体细胞突变，包括 TSC2 和 VHL 等肿瘤抑制基因，以及致癌途径的转录上调，包括 IGF-1、ERK/MAPK、PI3K/AKT 和 TGF-β。我们发现治疗后 HPD 肿瘤的免疫原性低于治疗前肿瘤，同时 ILC3 细胞（先天淋巴细胞的一个子集）的存在增加。我们还开发了预测 HPD 的基因表达特征。总之，我们确定了与 HPD 相关的基因组学和免疫特征，这可能有助于识别抗 PD-1 免疫治疗后面临不良临床结果风险的患者。抗 PD-1 治疗后超进展肿瘤中发生突变/表达变化 超进展肿瘤中免疫细胞群丰度模式发生变化 ILC3 细胞可能在抗 PD-1 治疗后在超进展肿瘤中富集 治疗后超进展肿瘤的免疫原性低于治疗前肿瘤 生理学 (170590663/189723279)；免疫学（186131996生理学；生物技术；细胞生物学；组学
Although PD-1-blocking immunotherapies demonstrate significant therapeutic promise, a subset of the patients could develop hyperprogressive disease (HPD) with accelerated tumor growth after anti-PD1 immunotherapy. To elucidate the underlying mechanisms, we compared the mutational and transcriptional landscapes between the pre- and post-therapy tumors of two patients developing HPD after anti-PD-1 immunotherapy. In post-therapy HPD tumors, somatic mutations were found in known cancer genes, including tumor suppressor genes such as TSC2 and VHL, along with transcriptional upregulation of oncogenic pathways, including IGF-1, ERK/MAPK, PI3K/AKT, and TGF-β. We found that post-therapy HPD tumors were less immunogenic than pre-therapy tumors, concurrent with an increased presence of ILC3 cells, a subset of innate lymphoid cells. We also developed a gene expression signature predictive of HPD. In summary, we identified the genomics and immune features associated with HPD, which may help identify patients at risk of adverse clinical outcome after anti-PD-1 immunotherapy. Mutations/expression changes occur in hyperprogressive tumors after anti-PD-1 therapy Immune cell population abundance pattern changed in the hyperprogressive tumors ILC3 cells may be enriched in the hyperprogressive tumors after anti-PD-1 therapy Post-therapy hyperprogressive tumors were less immunogenic than pre-therapy tumors Physiology (170590663/189723279); Immunology (186131996Physiology; Biotechnology; Cell Biology; Omics
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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：
5.8
作者：
Gu, Zuguang;Eils, Roland;Schlesner, Matthias
通讯作者：
Schlesner, Matthias
DOI：
10.1158/1078-0432.ccr-16-3133
发表时间：
2017-08-01
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
--
作者：
Kato S;Goodman A;Walavalkar V;Barkauskas DA;Sharabi A;Kurzrock R
通讯作者：
Kurzrock R
影响因子：
6.4
作者：
Kammerer-Jacquet, Solene-Florence;Crouzet, Laurence;Rioux-Leclercq, Nathalie
通讯作者：
Rioux-Leclercq, Nathalie
影响因子：
64.5
作者：
Hugo W;Zaretsky JM;Sun L;Song C;Moreno BH;Hu-Lieskovan S;Berent-Maoz B;Pang J;Chmielowski B;Cherry G;Seja E;Lomeli S;Kong X;Kelley MC;Sosman JA;Johnson DB;Ribas A;Lo RS
通讯作者：
Lo RS