Synergistic prognostic value of tumor-infiltrating lymphocytes and microvessel density in breast cancer

Breast cancer is a heterogeneous disease forming an intricate ecosystem, and its prognosis is affected by multiple factors, with the complexity of the tumor microenvironment (TME) being a pivotal determinant. Tumor-infiltrating lymphocytes (TILs) and microvessels, as key components of the TME, play a significant role in breast cancer prognosis. However, most studies focus on single biomarkers and ignore the synergistic effects among TME components. This study aimed to explore the associations of TILs and microvessel density-score (MVD-score) with the prognosis of breast cancer patients, and to analyze the correlations among different TILs types, MVD-score, and molecular subtypes of breast cancer. TILs-score and MVD-score were obtained from 471 patients using statistical analysis based on multiphoton microscopy (MPM) and their prognostic values were evaluated using Cox proportional hazards regression, receiver operating characteristic analysis, and Kaplan-Meier survival analysis. We further explored the correlation between different types of TILs, MVD-score, and molecular subtypes. The model combining TILs-score and MVD-score exhibited better prognostic performance, which may be sufficient to reflect the TME status. MVD-score was not statistically associated with TILs-score but was significantly associated with TILs-2 and TILs-3. Although MVD-score was not directly correlated with molecular subtypes, the association between MVD-score and types of TILs was modulated by molecular subtypes. MVD-score and TILs-score have predictive value for breast cancer prognosis. Their synergistic interaction within the TME, together with the modulatory effect of molecular subtypes, provides implications for deepening the understanding of TME complexity and guiding personalized treatment.