Precision Medicine Center, Seoul National University Bundang Hospital, Seongnamsi, Korea.
Genomic Medicine Institute (GMI), Medical Research Center, Seoul National University, Seoul, Republic of Korea.
Cancer Immunol Res. 2018 Jul;6(7):848-859. doi: 10.1158/2326-6066.CIR-17-0453. Epub 2018 May 2.
The immune microenvironment in lung squamous cell carcinoma (LUSC) is not well understood, with interactions between the host immune system and the tumor, as well as the molecular pathogenesis of LUSC, awaiting better characterization. To date, no molecularly targeted agents have been developed for LUSC treatment. Identification of predictive and prognostic biomarkers for LUSC could help optimize therapy decisions. We sequenced whole exomes and RNA from 101 tumors and matched noncancer control Korean samples. We used the information to predict subtype-specific interactions within the LUSC microenvironment and to connect genomic alterations with immune signatures. Hierarchical clustering based on gene expression and mutational profiling revealed subtypes that were either immune defective or immune competent. We analyzed infiltrating stromal and immune cells to further characterize the tumor microenvironment. Elevated expression of macrophage 2 signature genes in the immune competent subtype confirmed that tumor-associated macrophages (TAM) linked inflammation and mutation-driven cancer. A negative correlation was evident between the immune score and the amount of somatic copy-number variation (SCNV) of immune genes ( = -0.58). The SCNVs showed a potential detrimental effect on immunity in the immune-deficient subtype. Knowledge of the genomic alterations in the tumor microenvironment could be used to guide design of immunotherapy options that are appropriate for patients with certain cancer subtypes. .
肺鳞状细胞癌（LUSC）的免疫微环境尚未得到很好的理解，宿主免疫系统与肿瘤之间的相互作用，以及 LUSC 的分子发病机制，都有待更好地描述。迄今为止，尚未开发出针对 LUSC 治疗的分子靶向药物。鉴定用于 LUSC 的预测和预后生物标志物可能有助于优化治疗决策。我们对 101 个肿瘤和匹配的非癌症对照韩国样本进行了全外显子组和 RNA 测序。我们利用这些信息来预测 LUSC 微环境中特定于亚类的相互作用，并将基因组改变与免疫特征联系起来。基于基因表达和突变分析的层次聚类揭示了免疫缺陷或免疫功能正常的亚类。我们分析了浸润的基质和免疫细胞，以进一步描述肿瘤微环境。在免疫功能正常的亚类中，巨噬细胞 2 特征基因的高表达证实了肿瘤相关巨噬细胞（TAM）与炎症和突变驱动的癌症有关。免疫评分与免疫基因的体细胞拷贝数变异（SCNV）之间存在明显的负相关（= -0.58）。SCNV 在免疫缺陷亚类中对免疫有潜在的不利影响。对肿瘤微环境中基因组改变的了解可用于指导设计适合特定癌症亚类患者的免疫治疗方案。
