Faculty of Pharmaceutical Sciences, Department of Pharmacology and Physiology, Chulalongkorn University, Bangkok, Thailand.
Faculty of Pharmaceutical Sciences, Department of Biochemistry and Microbiology, Chulalongkorn University, Bangkok, Thailand.
PLoS One. 2022 Aug 12;17(8):e0273044. doi: 10.1371/journal.pone.0273044. eCollection 2022.
Triple-negative breast cancer (TNBC) is characterized by excessive accumulation of tumor-infiltrating immune cells, including tumor-associated macrophages (TAMs). TAMs consist of a heterogeneous population with high plasticity and are associated with tumor aggressiveness and poor prognosis. Moreover, breast cancer cells can secrete factors that influence TAM polarization. Therefore, this study aimed to evaluate the crosstalk between cancer cells and macrophages in the context of TNBC. Cytokine-polarized M2 macrophage were used as control. Distinct from the classical M2 macrophage, TAMs generated from TNBC-conditioned media upregulated both M1- and M2-associated genes, and secreted both the anti-inflammatory cytokine interleukin IL-10 and the proinflammatory cytokine IL-6 and tumor necrosis factor- α. Theses TNBC-induced TAMs exert aggressive behavior of TNBC cells. Consistently, TCGA and MTABRIC analyses of human breast cancer revealed upregulation of M1- associated genes in TNBC comparing with non-TNBC. Among these M1-associated genes, CXCL10 and IL1B were revealed to be independent prognostic factors for disease progression. In conclusion, TNBC cells induce macrophage polarization with a mixture of M1 and M2 phenotypes. These cancer-induced TAMs further enhance tumor cell growth and aggressiveness.
三阴性乳腺癌（TNBC）的特征是肿瘤浸润免疫细胞的过度积累，包括肿瘤相关巨噬细胞（TAMs）。TAMs 由具有高度可塑性的异质群体组成，与肿瘤侵袭性和预后不良有关。此外，乳腺癌细胞可以分泌影响 TAM 极化的因子。因此，本研究旨在评估 TNBC 中癌细胞与巨噬细胞之间的串扰。用细胞因子极化的 M2 巨噬细胞作为对照。与经典的 M2 巨噬细胞不同，来自 TNBC 条件培养基的 TAMs 上调了 M1 和 M2 相关基因，并分泌了抗炎细胞因子白细胞介素 IL-10 和促炎细胞因子 IL-6 和肿瘤坏死因子-α。这些 TNBC 诱导的 TAMs 表现出 TNBC 细胞的侵袭性行为。一致地，对人类乳腺癌的 TCGA 和 MTABRIC 分析显示，与非 TNBC 相比，TNBC 中上调了 M1 相关基因。在这些 M1 相关基因中，CXCL10 和 IL1B 被揭示为疾病进展的独立预后因素。总之，TNBC 细胞诱导巨噬细胞向 M1 和 M2 表型混合的极化。这些癌症诱导的 TAMs 进一步增强了肿瘤细胞的生长和侵袭性。
