High LAT1 Expression Is Associated With CD163 + Macrophage Infiltration and Poor Prognosis in Triple-Negative Breast Cancer

Abstract Background/Aim: Triple-negative breast cancer (TNBC) is an aggressive subtype that lacks targeted therapy, and robust prognostic biomarkers remain scarce. L-type amino acid transporter 1 (LAT1/SLC7A5) drives tumor amino acid metabolism and proliferation, whereas CD163+ M2-like tumor-associated macrophages (TAMs) constitute a hallmark of an immunosuppressive microenvironment. Patients and Methods: We investigated the expression, clinicopathological associations, and prognostic significance of tumor LAT1 and CD163+ macrophage density in 172 patients with TNBC. LAT1 and CD163 were assessed by immunohistochemistry and dichotomized at the cohort median. Results: High LAT1 expression was strongly associated with high histologic grade, larger tumor size, advanced stage, and elevated Ki-67 (all p<0.001) and predicted inferior overall survival (OS) and disease-free survival (DFS; both p<0.05). CD163+ macrophage density showed no association with conventional clinicopathological features. LAT1 and CD163 expression were weakly but significantly correlated (Pearson’s r=0.191, p=0.012; Spearman’s ρ=0.220, p=0.004). In multivariable analysis, the adjusted DFS associations of both markers were model-dependent: high CD163 was independently associated with DFS after adjustment for tumor size [hazard ratio (HR)=2.11, p=0.034] but only borderline after ordinal-stage adjustment (HR=1.87, p=0.076), and the LAT1 effect on DFS was likewise stage-dependent. For OS, high LAT1 remained independently prognostic after adjustment for stage and age (HR=3.6, p=0.02), whereas CD163 did not. Conclusion: These findings indicate that LAT1 and CD163 convey significant prognostic information in TNBC and support the further evaluation of LAT1-directed metabolic and macrophage-targeted therapeutic strategies.