Tumor Microenvironment-Mediated Immune Profiles Characterized by Distinct Survival Outcome and Immunotherapeutic Efficacy in Breast Cancer.
Tumor Microenvironment-Mediated Immune Profiles Characterized by Distinct Survival Outcome and Immunotherapeutic Efficacy in Breast Cancer.
复制标题
乳腺癌中以不同生存结果和免疫治疗效果为特征的肿瘤微环境介导的免疫特征
DOI：
10.3389/fgene.2022.840348
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发表时间：
2022
影响因子：
3.7
通讯作者：
Liu W
中科院分区：
文献类型：
--
作者：
Xu L;Hu Y;Liu W
背景：大量研究表明，肿瘤微环境（TME）与生存结局和治疗效果密切相关。然而，尚未对乳腺癌（BC）的TME特征进行全面调查。研究方法：在这里，我们基于TME细胞表达谱进行了共识聚类分析，以构建BC中TME模式簇和TME相关基因特征。GSVA结合CIBERSORT和ssGSEA算法分别用于评估生物学途径和免疫细胞浸润水平的差异。采用PCA方法构建TME评分，以量化个体BC患者中TME介导的模式水平。结果如下：我们在3,738个BC样本中确定了两个不同的TME基因簇，它们表现出不同的生存结果和丰富的生物过程。TME特征表明，这两个簇分别对应于已建立的免疫谱：热肿瘤表型和冷肿瘤表型。基于TME相关标签基因，我们构建了TME评分，并将BC患者分为低TME评分组和高TME评分组。具有高TME评分的患者表现出有利的结果和增加的免疫细胞浸润。进一步的研究显示，高TME评分还与免疫抑制分子的高表达、肿瘤突变负荷（TMB）降低和显著突变基因（SMG）的高突变率（例如，PIK 3CA和CDH 1）。结论：评估个体BC患者的TME介导的模式水平将有助于我们更好地理解BC患者对免疫疗法的反应，并指导更有效的免疫治疗方法。
Background: Numerous reports have highlighted that the tumor microenvironment (TME) is closely linked to survival outcome and therapeutic efficacy. However, a comprehensive investigation of the TME feature in breast cancer (BC) has not been performed. Methods: Here, we performed consensus clustering analysis based on TME cell expression profiles to construct TME pattern clusters and TME-related gene signature in BC. GSVA combined with CIBERSORT and ssGSEA algorithms were applied to evaluate the differences in biological pathway and immune cell infiltration level, respectively. The PCA method was employed to construct TME-score to quantify the TME-mediated pattern level in individual BC patients. Results: We determined two distinct TME gene clusters among 3,738 BC samples, which exhibited distinct survival outcome and enriched biological processes. The TME features demonstrated that these two clusters corresponded to the established immune profiles: hot and cold tumor phenotypes, respectively. Based on TME-related signature genes, we constructed the TME-score and stratified BC patients into low and high TME-score groups. Patients with high TME-score exhibited favorable outcome and increased infiltration of immune cells. Further investigation revealed that high TME-score was also related with high expression of immunosuppressive molecules, decreased tumor mutation burden (TMB), and high rate of mutation in significantly mutated genes (SMGs) (e.g., PIK3CA and CDH1). Conclusion: Assessing the TME-mediated pattern level of individual BC patients will assist us in better understanding the responses of BC patients to immunotherapies and directing more effective immunotherapeutic approaches.