Breast cancer, the most frequent female malignancy, is often curable when detected at an early stage. The treatment of metastatic breast cancer is more challenging and may be unresponsive to conventional therapy. Immunotherapy is crucial for treating metastatic breast cancer, but its resistance is a major limitation. The tumor microenvironment (TME) is vital in modulating the immunotherapy response. Various tumor microenvironmental components, such as cancer-associated fibroblasts (CAFs), tumor-associated macrophages (TAMs), and myeloid-derived suppressor cells (MDSCs), are involved in TME modulation to cause immunotherapy resistance. This review highlights the role of stromal cells in modulating the breast tumor microenvironment, including the involvement of CAF-TAM interaction, alteration of tumor metabolism leading to immunotherapy failure, and other latest strategies, including high throughput genomic screening, single-cell and spatial omics techniques for identifying tumor immune genes regulating immunotherapy response. This review emphasizes the therapeutic approach to overcome breast cancer immune resistance through CAF reprogramming, modulation of TAM polarization, tumor metabolism, and genomic alterations.

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乳腺癌肿瘤微环境的调节和免疫治疗耐药机制

乳腺癌是最常见的女性恶性肿瘤，如果在早期发现，通常是可以治愈的。转移性乳腺癌的治疗更具挑战性，并且可能对常规疗法没有反应。免疫疗法对于治疗转移性乳腺癌至关重要，但其耐药性是主要限制。肿瘤微环境（TME）对于调节免疫治疗反应至关重要。各种肿瘤微环境成分，例如癌症相关成纤维细胞 (CAF)、肿瘤相关巨噬细胞 (TAM) 和骨髓源性抑制细胞 (MDSC)，参与 TME 调节以引起免疫治疗耐药。本综述强调了基质细胞在调节乳腺肿瘤微环境中的作用，包括参与 CAF-TAM 相互作用、导致免疫治疗失败的肿瘤代谢改变以及其他最新策略，包括高通量基因组筛选、单细胞和空间组学识别调节免疫治疗反应的肿瘤免疫基因的技术。这篇综述强调了通过 CAF 重编程、TAM 极化调节、肿瘤代谢和基因组改变来克服乳腺癌免疫抵抗的治疗方法。