Department of Neurosurgery, The University of Texas M. D. Anderson Cancer Center, Houston, Texas, 77030.
Department of Bioinformatics and Computational Biology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas, 77030.
Cancer Immunol Res. 2013 Aug;1(2):112-22. doi: 10.1158/2326-6066.CIR-13-0028.
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.
胶质母细胞瘤的分子异质性已得到充分认识，并由此产生了分子定义的亚型。这些亚型（经典型、神经型、间质型和前神经型）与特定的信号通路和不同的患者生存相关。了解较少的是这些胶质母细胞瘤亚型与免疫系统效应器反应、免疫抑制以及肿瘤相关和肿瘤特异性抗原之间的相关性。随着越来越多的靶向肿瘤诱导免疫抑制的调节剂的新药物被开发出来，免疫系统的作用在治疗中变得越来越重要，而肿瘤诱导免疫抑制在胶质母细胞瘤中已有充分的记录。
为了确定抗原表达、免疫抑制和效应器反应基因在胶质母细胞瘤亚型中的关联，我们分析了癌症基因组图谱（TCGA）胶质母细胞瘤数据库。
我们发现间质型中存在大量与抗肿瘤促炎反应相关的基因，包括适应性和固有免疫以及免疫抑制。
这些结果表明，不同的神经胶质瘤抗原和免疫基因在胶质母细胞瘤亚型之间表现出不同的表达，这可能影响患者对免疫治疗策略的反应，具体取决于他们所携带的胶质母细胞瘤亚型。
