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Association of B7-H4, PD-L1, and tumor infiltrating lymphocytes with outcomes in breast cancer
B7-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 exp...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6288133/ https://www.ncbi.nlm.nih.gov/pubmed/30564631 http://dx.doi.org/10.1038/s41523-018-0095-1 |
Sumario: | B7-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. |
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