Department of Thyroid, Breast and Vascular Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an, China.
Department of Oncology, Shaanxi Provincial People's Hospital, Xi'an, China.
J Immunother. 2024;47(6):205-215. doi: 10.1097/CJI.0000000000000517. Epub 2024 Apr 30.
The involvement of M2-like tumor-associated macrophages (TAMs) in the advancement and treatment of cancer has been widely documented. This study aimed to develop a new signature associated with M2-like TAMs to predict the prognosis and treatment response in individuals diagnosed with breast cancer (BC). Weighted gene co-expression network analysis (WGCNA) was used to identity for M2-like TAM-related modular genes. The M2-like TAM-related modular subtype was identified using unsupervised clustering. WGCNA identified 722 M2-like TAM genes, 204 of which were associated with recurrence-free survival (RFS). Patients in cluster 1 exhibited upregulated cancer-related pathways, a higher proportion of triple-negative breast cancer (TNBC) subtypes, lower expression of immune checkpoints, and worse prognosis. Cluster 2 was characterized by upregulated immune-related pathways, a higher proportion of luminal A subtypes, and higher expression of immune checkpoints. A prognostic signature was created and confirmed using an independent dataset. A well-built nomogram can accurately forecast the survival outcomes for every individual. Furthermore, patients classified as low-risk exhibited a more favorable outlook, elevated tumor microenvironment (TME) score, and superior reaction to immunotherapy. In conclusion, we discovered 2 different types of M2-like TAMs and developed a prognostic signature revealing the diversity of M2-like TAMs in BC and their correlation with immune status and prognosis. This feature can predict the prognosis and immunotherapeutic effects of BC and offer novel concepts and approaches for tailoring BC treatment.
M2 样肿瘤相关巨噬细胞(TAMs)在癌症的进展和治疗中的作用已被广泛证实。本研究旨在开发一种与 M2 样 TAMs 相关的新标志物,以预测乳腺癌(BC)患者的预后和治疗反应。采用加权基因共表达网络分析(WGCNA)鉴定与 M2 样 TAM 相关的模块基因。采用无监督聚类鉴定 M2 样 TAM 相关模块亚型。WGCNA 鉴定出 722 个与 M2 样 TAM 相关的基因,其中 204 个与无复发生存(RFS)相关。簇 1 中的患者表现出上调的癌症相关通路,更高比例的三阴性乳腺癌(TNBC)亚型,更低的免疫检查点表达,以及更差的预后。簇 2 的特征是上调的免疫相关通路,更高比例的 luminal A 亚型,以及更高的免疫检查点表达。使用独立数据集构建并验证了预后标志物。一个精心构建的列线图可以准确预测每个个体的生存结局。此外,低危患者表现出更好的预后,更高的肿瘤微环境(TME)评分,以及对免疫治疗的更优反应。总之,我们发现了 2 种不同类型的 M2 样 TAMs,并开发了一种预后标志物,揭示了 BC 中 M2 样 TAMs 的多样性及其与免疫状态和预后的相关性。这一特征可以预测 BC 的预后和免疫治疗效果,并为 BC 治疗的个体化提供新的概念和方法。