Tumor Microenvironment in Triple-Negative Breast Cancer and Targeting Approaches

Authors

  • Youli Li Department of Medical Oncology, Fudan University Shanghai Cancer Center Xiamen Hospital, Xiamen, China https://orcid.org/0000-0003-3644-3930
  • Yang Chen Phase I Unit, Fudan University Shanghai Cancer Center, Shanghai, China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China. https://orcid.org/0000-0003-2162-3648
  • Yuxin Mu Phase I Unit, Fudan University Shanghai Cancer Center, Shanghai, China. Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China https://orcid.org/0000-0002-8465-6933
  • Xuemei Xiu Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China; Department of Oncology, The Second People's Hospital of Kashi, Kashi, Xinjiang, China. https://orcid.org/0009-0007-1031-0503
  • Wenxing Qin Department of Medical Oncology, Fudan University Shanghai Cancer Center Xiamen Hospital, Xiamen, China; Phase I Unit, Fudan University Shanghai Cancer Center, Shanghai, China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China. https://orcid.org/0009-0002-7274-4917

Keywords:

Tumor microenvironment, triple-negative breast cancer, targeted therapy , immune checkpoint inhibitors, Drug resistance, Biomarkers

Abstract

Triple-negative breast cancer (TNBC) is an aggressive and heterogeneous subtype of breast cancer with high recurrence and early metastasis. Unlike hormone receptor-positive or HER2-positive cancers, TNBC lacks targeted therapies, and standard chemotherapy often yields limited and transient responses, making treatment challenging. The tumor microenvironment (TME) plays a central role in TNBC progression, immune evasion, and therapy resistance. It comprises multiple cellular components, tumor-associated macrophages (TAMs), cancer-associated fibroblasts (CAFs), tumor-infiltrating lymphocytes (TILs), and myeloid-derived suppressor cells (MDSCs), as well as structural and signaling elements such as the extracellular matrix (ECM), growth factors, and cytokines. Interactions among these components create an immunosuppressive, pro-tumorigenic milieu that supports cancer cell survival, invasion, and metastasis. Targeting the TME has emerged as a promising therapeutic strategy. Immunotherapies, particularly immune checkpoint inhibitors (ICIs), can restore antitumor immunity by reversing T cell exhaustion and mitigating immune suppression. Response rates remain variable, leading to the exploration of combination approaches that pair ICIs with chemotherapy, radiotherapy, or TME-modulating agents to enhance efficacy. Direct targeting of TME components, including CAFs, TAMs, MDSCs, and ECM remodeling enzymes, is also being developed to disrupt the supportive tumor niche and enhance drug delivery. This review provides a comprehensive overview of the TNBC TME, emphasizing its role in tumor progression and therapy resistance, and summarizes current and emerging strategies to target the TME. By clarifying complex cellular and molecular interactions, these approaches aim to sensitize tumors to therapy, prevent metastasis, and support the development of more effective, personalized treatments for TNBC.

Author Biographies

Youli Li, Department of Medical Oncology, Fudan University Shanghai Cancer Center Xiamen Hospital, Xiamen, China

Department of Medical Oncology, Fudan University Shanghai Cancer Center Xiamen Hospital, Xiamen, China

Yang Chen, Phase I Unit, Fudan University Shanghai Cancer Center, Shanghai, China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.

Phase I Unit, Fudan University Shanghai Cancer Center, Shanghai, China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.

Xuemei Xiu, Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China; Department of Oncology, The Second People's Hospital of Kashi, Kashi, Xinjiang, China.

Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China; Department of Oncology, The Second People's Hospital of Kashi, Kashi, Xinjiang, China.

Wenxing Qin, Department of Medical Oncology, Fudan University Shanghai Cancer Center Xiamen Hospital, Xiamen, China; Phase I Unit, Fudan University Shanghai Cancer Center, Shanghai, China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.

Department of Medical Oncology, Fudan University Shanghai Cancer Center Xiamen Hospital, Xiamen, China; Phase I Unit, Fudan University Shanghai Cancer Center, Shanghai, China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.

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Breast Cancer TME Targeted Therapies.

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Li Y, Chen Y, Mu Y, Xiu X, Qin W. Tumor Microenvironment in Triple-Negative Breast Cancer and Targeting Approaches. cbtt [Internet]. 2025 Dec. 16 [cited 2025 Dec. 23];:1-31. Available from: https://www.cancerbiometherapy.com/index.php/cbtt/article/view/5

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