Background: Tumor microenvironment (TME) cells play important roles in tumor progression. Accumulating evidence show that they can be exploited to predict the clinical outcomes and therapeutic responses of the tumor. However, the role of immune genes of TME in small cell lung cancer (SCLC) is currently unknown.

Objective: To determine the role of immune genes in SCLC.

Methods: We downloaded the expression profile and clinical follow-up data of SCLC patients from Gene Expression Omnibus (GEO), and TME infiltration profile data of 158 patients using CIBERSORT. The correlation between TME phenotypes, genomic features, and clinicopathological features of SCLC was examined. A gene signature was constructed based on TME genes to further evaluate the relationship between molecular subtypes of SCLC with the prognosis and clinical features.

Results: We identified a group of genes that are highly associated with TME. Several immune cells in TME cells were significantly correlated with SCLC prognosis (p<0.0001). These immune cells displayed diverse immune patterns. Three molecular subtypes of SCLC (TMEC1-3) were identified on the basis of enrichment of immune cell components, and these subtypes showed dissimilar prognosis profiles (p=0.03). The subtype with the best prognosis, TMEC3, was enriched with immune activation factors such as oncogene M0, oncogene M2, T cells follicular helper, and T cells CD8 (p<0.001). The TMEC1 subtype with the worst prognosis was enriched with T cells CD4 naive, B cells memory and Dendritic cells activated cells (p<0.001). Further analysis showed that the TME was significantly enriched with immune checkpoint genes, immune genes, and immune pathway genes (p<0.01). From the gene expression data, we identified four TME-related genes, GZMB, HAVCR2, PRF1 and TBX2, which were significantly associated with poor prognosis in both the training set and the validation set (p<0.05). These genes may serve as markers for monitoring tumor responses to immune checkpoint inhibitors.

Conclusion: This study shows that TME features may serve as markers for evaluating the response of SCLC cells to immunotherapy.

背景：肿瘤微环境（TME）细胞在肿瘤进展中起重要作用。越来越多的证据表明，可以利用它们来预测肿瘤的临床结果和治疗反应。然而，目前尚不清楚TME免疫基因在小细胞肺癌（SCLC）中的作用。

目的：确定免疫基因在SCLC中的作用。

方法：我们使用CIBERSORT从Gene Expression Omnibus（GEO）下载了SCLC患者的表达谱和临床随访数据，以及158例患者的TME浸润谱数据。检查了TML表型，基因组特征和SCLC临床病理特征之间的相关性。基于TME基因构建基因签名，以进一步评估SCLC分子亚型与预后和临床特征之间的关系。

结果：我们鉴定了一组与TME高度相关的基因。TME细胞中的几个免疫细胞与SCLC的预后显着相关（p <0.0001）。这些免疫细胞显示出多种免疫模式。在免疫细胞成分富集的基础上，鉴定了三种SCLC分子亚型（TMEC1-3），这些亚型显示出不同的预后特征（p = 0.03）。预后最好的亚型TMEC3富含免疫激活因子，例如癌基因M0，癌基因M2，T细胞滤泡辅助细胞和T细胞CD8（p <0.001）。预后最差的TMEC1亚型富含T细胞CD4天真，B细胞记忆和树突状细胞活化细胞（p <0.001）。进一步的分析表明，TME明显富含免疫检查点基因，免疫基因，和免疫途径基因（p <0.01）。从基因表达数据中，我们鉴定了四个与TME相关的基因GZMB，HAVCR2，PRF1和TBX2，它们与训练组和验证组的不良预后显着相关（p <0.05）。这些基因可以用作监测肿瘤对免疫检查点抑制剂反应的标志物。

结论：这项研究表明，TME的特征可能是评估SCLC细胞对免疫治疗反应的标志。