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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 |
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author | Altan, Mehmet Kidwell, Kelley M. Pelekanou, Vasiliki Carvajal-Hausdorf, Daniel E. Schalper, Kurt A. Toki, Maria I. Thomas, Dafydd G. Sabel, Michael S. Hayes, Daniel F. Rimm, David L. |
author_facet | Altan, Mehmet Kidwell, Kelley M. Pelekanou, Vasiliki Carvajal-Hausdorf, Daniel E. Schalper, Kurt A. Toki, Maria I. Thomas, Dafydd G. Sabel, Michael S. Hayes, Daniel F. Rimm, David L. |
author_sort | Altan, Mehmet |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-6288133 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-62881332018-12-18 Association of B7-H4, PD-L1, and tumor infiltrating lymphocytes with outcomes in breast cancer Altan, Mehmet Kidwell, Kelley M. Pelekanou, Vasiliki Carvajal-Hausdorf, Daniel E. Schalper, Kurt A. Toki, Maria I. Thomas, Dafydd G. Sabel, Michael S. Hayes, Daniel F. Rimm, David L. NPJ Breast Cancer Article 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. Nature Publishing Group UK 2018-12-10 /pmc/articles/PMC6288133/ /pubmed/30564631 http://dx.doi.org/10.1038/s41523-018-0095-1 Text en © The Author(s) 2018 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article Altan, Mehmet Kidwell, Kelley M. Pelekanou, Vasiliki Carvajal-Hausdorf, Daniel E. Schalper, Kurt A. Toki, Maria I. Thomas, Dafydd G. Sabel, Michael S. Hayes, Daniel F. Rimm, David L. Association of B7-H4, PD-L1, and tumor infiltrating lymphocytes with outcomes in breast cancer |
title | Association of B7-H4, PD-L1, and tumor infiltrating lymphocytes with outcomes in breast cancer |
title_full | Association of B7-H4, PD-L1, and tumor infiltrating lymphocytes with outcomes in breast cancer |
title_fullStr | Association of B7-H4, PD-L1, and tumor infiltrating lymphocytes with outcomes in breast cancer |
title_full_unstemmed | Association of B7-H4, PD-L1, and tumor infiltrating lymphocytes with outcomes in breast cancer |
title_short | Association of B7-H4, PD-L1, and tumor infiltrating lymphocytes with outcomes in breast cancer |
title_sort | association of b7-h4, pd-l1, and tumor infiltrating lymphocytes with outcomes in breast cancer |
topic | Article |
url | 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 |
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