Immunohistological analysis of B7-H4, IDO1, and PD-L1 expression and tumor immune microenvironment based on triple-negative breast cancer subtypes

Abstract Background: B7-H4 and indoleamine 2,3-dioxygenase (IDO1) are factors involved in the inhibition of antitumor activity and are new therapeutic targets for immune checkpoint therapy. However, the category of patients wherein these factors are highly expressed and how they are related to each other and programmed cell death ligand 1 (PD-L1) are not yet fully clear. Methods: Immunostaining for PD-L1, B7-H4, and IDO1 was performed on whole-slide sections of 119 cases of triple-negative breast cancer (TNBC). TNBC subtypes were also determined by immunohistochemistry analysis of cytokeratin 5/6 and androgen receptor (AR) expression. The tumor immune microenvironment was evaluated based on stromal tumor-infiltrating lymphocytes (sTILs) (%), pattern classification of TILs, tumor stromal ratio, and tertiary lymphoid structure. Immunostaining for CD8 and FOXP3 was also performed. Results: B7-H4 expression was significantly high in cases with a combined positive score cutoff of 5 for PD-L1 (clone 28-8) (p = 0.021). The H-scores of AR and B7-H4 were inversely correlated (ρ = -0.509, p < 0.001). AR expression was high in cases with IDO1 < 1% (p = 0.046), while B7H4 and IDO1 expression levels were inversely correlated in cases with AR <10% (ρ = -0.354, p < 0.001). Conclusions: In the population of TNBC, B7-H4 and PD-L1 expression were exclusively related to AR expression.B7-H4 and IDO1 expression was exclusive in the non-luminal androgen receptor subtype of TNBC. These trends in expression may help in the future selection of antiandrogenic agents and immune checkpoint inhibitors for patient treatment.