CTL-NK Signature Based on Immune Gene Profiling and IHC Predicts Clinical Outcomes in Triple-Negative Breast Cancer.

AIM: Triple-negative breast cancer (TNBC) lacks targeted therapies and demonstrates heterogeneous outcomes. Tumor-infiltrating lymphocytes (TILs) are candidate prognostic biomarkers that reflect the tumor immune microenvironment. This study evaluated the prognostic value of cytotoxic T lymphocytes (CTLs) and natural killer (NK) cells, with emphasis on granulysin (GNLY) and granzyme B (GZMB), in TNBC.

MATERIALS & METHODS: We combined NanoString immune gene profiling with whole-slide immunohistochemistry (IHC) in a TNBC cohort (n = 155). Quantitative and spatial analyses were performed to assess CTL and NK cell infiltration and their associations with clinicopathological features and survival outcomes.

RESULTS: High TIL density (≥10%) and elevated CTL-NK scores (≥2) correlated with lower tumor stage, absence of lymphovascular invasion (LVI), and favorable immune subset ratios (all p < 0.05). In multivariable analysis, absence of LVI, high CD4+ and CD8+ infiltration, and CTL-NK score ≥2 independently predicted improved disease-free survival (DFS; hazard ratio [HR] range 0.45-0.62, all p < 0.05). CD4+ infiltration demonstrated the strongest prognostic effect, while CD8+ infiltration and the CTL-NK score also conferred independent benefit.

CONCLUSION: Quantitative and spatial assessment of CTL and NK infiltration provides independent prognostic information in TNBC. The CTL-NK score can be integrated into routine pathology and may refine risk stratification, supporting personalized immunotherapy strategies.