Core Viewpoint - The study highlights the role of interferon-induced CD8+ T cell senescence as a driving factor for immune therapy resistance in early triple-negative breast cancer (TNBC), suggesting that nicotinamide mononucleotide (NMN) treatment may restore T cell function and enhance the benefits of immune checkpoint blockade therapy [4][5][8]. Group 1: TNBC Characteristics and Treatment Challenges - TNBC is defined by the absence or low expression of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2), characterized by higher recurrence rates and shorter overall survival in patients [3]. - Chemotherapy remains the primary systemic treatment for TNBC due to the lack of specific therapeutic targets, but its efficacy is limited to a subset of patients [3]. Group 2: Research Findings on T Cell Senescence - A study published in Science Translational Medicine found that interferon (IFN)-induced CD8+ T cells reduce the efficacy of anti-PD-1 immunotherapy in early TNBC patients and preclinical models [4][5]. - The research identified a group of enriched IFN-induced CD8+ T cells in early TNBC samples that predict non-responsiveness to immunotherapy, driven by HLA-DR+ monocyte-derived IFN leading to T cell senescence [6]. Group 3: Potential Therapeutic Strategies - Treatment with NMN, a precursor of NAD+, was shown to restore the function of senescent CD8+ T cells and enhance the effects of immunotherapy in both patient-derived organoid-T cell co-cultures and mouse models [5][6][8]. - The findings suggest that targeting T cell senescence could be a promising strategy to improve immunotherapy outcomes in early TNBC [8].