Tumor-infiltrating lymphocytes are associated with β -catenin overexpression in breast cancer

BACKGROUND: Inhibition of lymphocytes infiltration and activity may impair antitumor immune response and limit treatment responsiveness. Wnt/β-catenin pathway has been suggested to contribute to immune evasion in tumor by suppressing the function of immune cells and excluding T cell infiltration. However, the effects of Wnt/β-catenin on TILs recruitment remain controversial. OBJECTIVE: We aimed to investigate whether intratumoral Wnt/β-catenin signaling could affect the lymphocyte infiltration in breast cancer. METHODS: The distribution of stromal TILs, CD8+ and FOXP3+ TIL subsets, and the expression of β-catenin were separately assessed on consecutive sections of 96 breast cancer specimens. RESULTS: Both stromal infiltrated TILs and β-catenin expression were upregulated in hormone receptor negative HER2-enriched and TNBC subtypes. Furthermore, high levels of stromal TILs as well as CD8+ or FOXP3+ TIL subsets were associated with β-catenin overexpression by breast cancer, respectively. CONCLUSIONS: For the first time, we demonstrated that rather than excluding lymphocytes infiltration as reported in mela-noma, high levels of TILs were associated with β-catenin overexpression in BC. Wnt/β-catenin signaling may play a critical role in BC immunity, particularly in HER2-enriched and triple negative BC, and may serve as a potential target for regulating immune infiltrates in breast cancer.