Immune heterogeneity of glioblastoma subtypes: extrapolation from the cancer genome atlas.
Immune heterogeneity of glioblastoma subtypes: extrapolation from the cancer genome atlas.
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DOI：
10.1158/2326-6066.cir-13-0028
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发表时间：
2013-08
影响因子：
10.1
通讯作者：
Heimberger AB
中科院分区：
文献类型：
--
作者：
Doucette T;Rao G;Rao A;Shen L;Aldape K;Wei J;Dziurzynski K;Gilbert M;Heimberger AB
胶质母细胞瘤的分子异质性已被充分认识，并导致产生分子定义的亚型。这些亚型（经典型、神经型、间充质型和前神经型）与特定的信号通路和不同的患者生存率相关。较少了解的是这些胶质母细胞瘤亚型与免疫系统效应反应，免疫抑制和肿瘤相关和肿瘤特异性抗原之间的相关性。免疫系统的作用正变得越来越与治疗相关，因为正在开发新的药剂以靶向肿瘤诱导的免疫抑制的介质，这在胶质母细胞瘤中有充分的记载。为了确定胶质母细胞瘤亚型中抗原表达、免疫抑制和效应反应基因的相关性，我们分析了癌症基因组图谱（TCGA）胶质母细胞瘤数据库。我们发现间充质亚型内的基因富集反映了抗肿瘤促炎反应，包括适应性和先天免疫以及免疫抑制。这些结果表明，不同的胶质瘤抗原和免疫基因表现出胶质母细胞瘤亚型之间的差异表达，这可能会影响患者的免疫治疗策略的反应，这取决于他们所携带的胶质母细胞瘤的亚型。
The molecular heterogeneity of glioblastoma has been well recognized and has resulted in the generation of molecularly defined subtypes. These subtypes (classical, neural, mesenchymal, and proneural) are associated with particular signaling pathways and differential patient survival. Less understood is the correlation between these glioblastoma subtypes with immune system effector responses, immune suppression and tumor-associated and tumor-specific antigens. The role of the immune system is becoming increasingly relevant to treatment as new agents are being developed to target mediators of tumor-induced immune suppression which is well documented in glioblastoma. To ascertain the association of antigen expression, immune suppression, and effector response genes within glioblastoma subtypes, we analyzed the Cancer Genome Atlas (TCGA) glioblastoma database. We found an enrichment of genes within the mesenchymal subtype that are reflective of anti-tumor proinflammatory responses, including both adaptive and innate immunity and immune suppression. These results indicate that distinct glioma antigens and immune genes demonstrate differential expression between glioblastoma subtypes and this may influence responses to immune therapeutic strategies in patients depending on the subtype of glioblastoma they harbor.