Abstract PS2-10-25: Combined T and B cell signatures as prognostic biomarkers in triple-negative breast cancer (TNBC)

Abstract Background: CD8+ T cells infiltration is a known predictor of improved outcomes in patients with triple-negative breast cancer (TNBC). However, the contribution of coordinated T cell and B cell immune interactions within the tumor microenvironment (TME), remains to be fully explored. We posit that dual expression of T cell (IFNy, CD40LG) and B cell (CD19, CD40) markers would associate with patient survival and more favorable immune landscape in TNBC. In this study, we evaluate the prognostic relevance of dual expression of IFNy/CD19 and CD40/CD40LG in TNBC and its association with TME. Methods: 3,662 TNBC samples were analyzed by NGS (592, NextSeq; WES/WTS, NovaSeq; Caris Life Sciences, Phoenix, AZ). Dual expression groups IFNy/CD19-high (n=1275), IFNy/CD19-low (n=1272), IFNy-high/CD19-low (n=558), IFNy-low/CD19-high (n=557), CD40LG/CD40-high (n=1303), CD40LG/CD40-low (n=1303), CD40LG-high/CD40-low (n=529) and CD40LG-low/CD40-high (n=529) were classified by RNA expression above or below the 50th percentile. Immune cells were estimated using WTS deconvolution (Quantiseq). Real-world median overall survival (mOS) was derived from insurance claims and calculated from biopsy to last contact using Kaplan-Meier. Statistical significance was assessed using chi-square and Mann-Whitney U with multiple comparison adjustments (q0.05). Results: Patients with TNBC with IFNy/CD19-high tumors exhibited longer mOS (28 months (m) vs 16.1 m, HR 0.6, 95% CI 0.55- 0.66, p0.00001) compared to those with IFNy/CD19-low. Dual high-expression (IFNy/CD19-high) had higher mOS compared to the other subgroups, namely IFNy-high/CD19-low (28 m vs 20 m, HR 0.76, 95% CI 0.67-0.86, p0.0001), IFNy-low/CD19-high (28 m vs 19.1 m, HR 0.7, 95% CI 0.62-0.79, p0.00001). A similar pattern was observed for the CD40/CD40LG-high that exhibited longer mOS (27 m vs 17.9 m, HR 0.68, 95% CI 0.61-0.74, p0.00001) compared to those with CD40/CD40LG-low. Also, dual CD40/CD40LG-high had higher mOS compared to CD40-high/CD40LG-low (27 m vs 17.2 m, HR 0.7, 95% CI 0.62-0.8, p0.00001), CD40-low/CD40LG-high (27 m vs 19 m, HR 0.7, 95% CI 0.62-0.8, p0.00001). These dual high-expression tumors were enriched for diverse immune cell populations, including B cells, dendritic cells (DC), M1 MΦ, M2 MΦ, natural killer (NK) cells, CD8+ T cells, all q0.05. Moreover, dual high group had higher levels of immune checkpoint genes CD274, PDCD1, CTLA4, HAVCR2 (TIM3), LAG3, TIGIT and CD47, all q0.05 (Table), suggesting a highly active yet potentially exhausted immune microenvironment. Conclusions: Coordinated expression of T and B cell markers identifies a subset of TNBC with enhanced immune infiltration and improved survival, underscoring the prognostic significance for T-B cell crosstalk. These findings highlight the potential of combined immune signatures to inform prognosis and guide immunotherapeutic strategies in TNBC. Citation Format: S. Gandhi, S. Kumar Deshmukh, S. Wu, J. Xiu, G. Sledge Jr., E. Roussos Torres, M. B. Lustberg, M. Opyrchal, S. Yao, K. Takabe, M. Ernstoff, M. Abdelbary, A. T Ruffin, A. C Cole, H. M. Knochelmann, K. Kalinsky, G. B. Lesinski, C. M. Paulos. Combined T and B cell signatures as prognostic biomarkers in triple-negative breast cancer (TNBC) abstract. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr PS2-10-25.