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<p>The cardinal features of triple-negative breast cancer (TNBC) are that it is aggressive and does not express estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2, presenting significant therapeutic challenges. Recent advances have identified immune checkpoint inhibitors (ICIs), especially anti-PD-1/PD-L1 agents, as promising treatments for TNBC. Tumor mutational burden (TMB) has been implicated as a promising approach for predicting ICI responses. This review examines the current evidence in favor of TMB as a biomarker, its relationship with ICI efficacy, and future directions in TNBC therapy. We explore the mechanisms linking high TMB to enhanced neoantigen presentation, which leads to improved immune responses and better patient outcomes with ICIs. Additionally, we discuss the role of combination therapies involving ICIs with chemotherapy or poly(ADP-ribose) polymerase inhibitors, and how TMB can guide treatment personalization in TNBC. While TMB shows promise, further research is needed to establish standardized measurement techniques and cutoffs, enhancing its clinical utility in predicting ICI response. Future studies focusing on tumor microenvironment interactions and resistance mechanisms are crucial for advancing precision oncology in TNBC.</p> Graphical abstract <p></p>

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TMB as a predictive biomarker for ICI response in TNBC: current evidence and future directions for augmented anti-tumor responses

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年11月18日

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  • Rajdeep Das,
  • Sneha Deb,
  • P. K. Suresh

摘要

The cardinal features of triple-negative breast cancer (TNBC) are that it is aggressive and does not express estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2, presenting significant therapeutic challenges. Recent advances have identified immune checkpoint inhibitors (ICIs), especially anti-PD-1/PD-L1 agents, as promising treatments for TNBC. Tumor mutational burden (TMB) has been implicated as a promising approach for predicting ICI responses. This review examines the current evidence in favor of TMB as a biomarker, its relationship with ICI efficacy, and future directions in TNBC therapy. We explore the mechanisms linking high TMB to enhanced neoantigen presentation, which leads to improved immune responses and better patient outcomes with ICIs. Additionally, we discuss the role of combination therapies involving ICIs with chemotherapy or poly(ADP-ribose) polymerase inhibitors, and how TMB can guide treatment personalization in TNBC. While TMB shows promise, further research is needed to establish standardized measurement techniques and cutoffs, enhancing its clinical utility in predicting ICI response. Future studies focusing on tumor microenvironment interactions and resistance mechanisms are crucial for advancing precision oncology in TNBC.

Graphical abstract