Combining the guidelines and multiphoton imaging methods to improve the prognostic value of tumor-infiltrating lymphocytes in breast cancer

Multiphoton microscopy (MPM) was introduced to label-freely obtain tumor-infiltrating lymphocytes (TILs) images from a total of 611 patients, and the prognostic value of TILs in breast cancer was assessed by the MPM method (TILs-MPM) and guidelines method proposed by the International Immuno-Oncology Biomarker Working Group (TILs-WG), respectively. Moreover, the clinical (CLI) model, TILs-WG + TILs-MPM model, and full model (CLI + TILs-WG + TILs-MPM) were developed to investigate the prognostic value of TILs. The results show that TILs-WG performs better in estrogen receptor (ER)-negative subgroup, and TILs-MPM is comparable with TILs-WG in the ER-negative subgroup, but has the best performance in the ER-positive subgroup. Furthermore, the TILs-WG + TILs-MPM model can significantly improve the prognostic power compared with the TILs-WG model, and the full model has excellent performance, with high area under the curve (AUC) and hazard ratio (HR) in both ER-positive, ER-negative subgroups, and the complete cohort. Our results suggest that the combination of TILs-WG with TILs-MPM model can greatly improve the prognostic value of TILs.