Altan, MehmetKidwell, Kelley M.Pelekanou, VasilikiSchalper, Kurt A.Toki, María I.Thomas, Dafydd G.Sabel, Michael S.Hayes, Daniel F.Rimm, David L.Carvajal-Hausdorf, Daniel2022-05-022022-05-022018Altan, M., Kidwell, K.M., Pelekanou, V. et al. Association of B7-H4, PD-L1, and tumor infiltrating lymphocytes with outcomes in breast cancer. npj Breast Cancer 4, 40 (2018). https://doi.org/10.1038/s41523-018-0095-1https://doi.org/10.1038/s41523-018-0095-1http://hdl.handle.net/11447/6040B7-H4 (VTCN1) is a member of the CD28/B7 family of immune co-inhibitory molecules. The relationship of tumor and stromal B7-H4 protein expression with PD-L1, tumor infiltrating lymphocytes (TILs) and its association with clinico-pathological variables are not well defined. Herein, we explore the expression level of B7-H4 protein in breast cancer and evaluate its association with TILs, levels of PD-L1 expression, and clinico-pathological characteristics in two independent populations. In this study, we used multiplexed automated quantitative immunofluorescence (QIF) to measure the levels of B7-H4 and PD-L1 protein and determined TILs through pathologist assessment of H&E-stained preparations in over a thousand breast cancer cases from two institutions represented in tissue microarray format. Associations between the marker levels, major clinico-pathological variables, and survival were analyzed. We detected B7-H4 protein was highly expressed in both breast cancer and stromal cells. Its expression was independent of breast cancer intrinsic subtypes. PD-L1 expression was higher in triple negative breast cancers. Neither B7-H4 nor PD-L1 were associated with survival in breast cancer. Our study shows there is a mutually exclusive pattern of B7-H4 with both tumor PD-L1 expression and TILs in all breast cancers, independent of breast cancer intrinsic subtype. This exclusive pattern suggests that some breast tumors may preferentially use one B7-related immune evasion mechanism/pathway. This could explain the clinical benefit that is seen only in a fraction of patients with immune checkpoint inhibitors directed exclusively towards PD-L1 in breast cancer.enBreast cancerTumour immunologyArticle