School of Biotechnology, KIIT Deemed to be University, Bhubaneswar, 751024, India.
Department of Pharmaceutical Technology, Brainware University, West Bengal, 700125, India.
Mol Cancer. 2024 May 7;23(1):92. doi: 10.1186/s12943-024-01990-4.
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.
乳腺癌是最常见的女性恶性肿瘤，早期发现通常可治愈。转移性乳腺癌的治疗更具挑战性，可能对常规治疗无反应。免疫疗法对于治疗转移性乳腺癌至关重要，但它的耐药性是一个主要的限制。肿瘤微环境（TME）在调节免疫疗法反应中起着至关重要的作用。各种肿瘤微环境成分，如癌症相关成纤维细胞（CAFs）、肿瘤相关巨噬细胞（TAMs）和髓系来源的抑制细胞（MDSCs），参与 TME 的调节以导致免疫疗法耐药性。这篇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 CAF-TAM 相互作用的参与、肿瘤代谢的改变导致免疫疗法失败，以及其他最新的策略，包括高通量基因组筛选、单细胞和空间组学技术，用于识别调节免疫疗法反应的肿瘤免疫基因。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耐药性的治疗方法。
