Association of B7-H4, PD-L1, and tumor infiltrating lymphocytes with outcomes in breast cancer View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2018-12

AUTHORS

Mehmet Altan, Kelley M. Kidwell, Vasiliki Pelekanou, Daniel E. Carvajal-Hausdorf, Kurt A. Schalper, Maria I. Toki, Dafydd G. Thomas, Michael S. Sabel, Daniel F. Hayes, David L. Rimm

ABSTRACT

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. More... »

PAGES

40

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/s41523-018-0095-1

DOI

http://dx.doi.org/10.1038/s41523-018-0095-1

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1110346414

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/30564631


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Turtle is a human-readable linked data format.

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RDF/XML is a standard XML format for linked data.

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