Immune checkpoint molecules B7-H6 and PD-L1 co-pattern the tumor inflammatory microenvironment in human breast cancer

Abstract B7-H6 and PD-L1 belong to the B7 family co-stimulatory molecules fine-tuning the immune response. The present work investigates the clinical effect of B7-H6 protein expression with PD-L1 status and the infiltration of natural killer cells as potential biomarkers in breast tumor inflammatory...

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Autores principales: Boutheina Cherif, Hana Triki, Slim Charfi, Lobna Bouzidi, Wala Ben Kridis, Afef Khanfir, Kais Chaabane, Tahya Sellami-Boudawara, Ahmed Rebai
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Publicado: Nature Portfolio 2021
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Acceso en línea:https://doaj.org/article/e0f66d5c1c884bce981019b3b9ea42ee
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spelling oai:doaj.org-article:e0f66d5c1c884bce981019b3b9ea42ee2021-12-02T18:15:24ZImmune checkpoint molecules B7-H6 and PD-L1 co-pattern the tumor inflammatory microenvironment in human breast cancer10.1038/s41598-021-87216-92045-2322https://doaj.org/article/e0f66d5c1c884bce981019b3b9ea42ee2021-04-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-87216-9https://doaj.org/toc/2045-2322Abstract B7-H6 and PD-L1 belong to the B7 family co-stimulatory molecules fine-tuning the immune response. The present work investigates the clinical effect of B7-H6 protein expression with PD-L1 status and the infiltration of natural killer cells as potential biomarkers in breast tumor inflammatory microenvironment. The expression levels of B7-H6 protein by cancer cells and immune infiltrating cells in human breast cancer tissues and evaluate their associations with PD-L1 expression, NK cell status, clinical pathological features and prognosis were explored. The immunohistochemistry labeling method was used to assess B7-H6 and PD-L1 proteins expression by cancer and immune cells. The associations between immune checkpoint, major clinical pathological variables and survival rates were analyzed. B7-H6 protein was depicted in both breast and immune cells. Results showed that Tumor B7-H6 expression is highly associated with Her-2 over expression. B7-H6 + immune cells are highly related to the Scarff–Bloom–Richardson grade and associated with PD-L1 expression and NK cells status. Survival analysis revealed a better prognosis in patients with low expression of B7-H6 by cancer cells. Conversely, B7-H6 + immune cells were significantly associated with longer survival. Findings strongly suggest an interaction between B7 molecules that contributes to a particular design of the inflammatory microenvironment. This may influence the efficiency of therapies based on antibodies blocking the PD-L1/PD1 pathway and can explain the detection of clinical benefits only in a fraction of patients treated with immune checkpoint inhibitors.Boutheina CherifHana TrikiSlim CharfiLobna BouzidiWala Ben KridisAfef KhanfirKais ChaabaneTahya Sellami-BoudawaraAhmed RebaiNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-13 (2021)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Boutheina Cherif
Hana Triki
Slim Charfi
Lobna Bouzidi
Wala Ben Kridis
Afef Khanfir
Kais Chaabane
Tahya Sellami-Boudawara
Ahmed Rebai
Immune checkpoint molecules B7-H6 and PD-L1 co-pattern the tumor inflammatory microenvironment in human breast cancer
description Abstract B7-H6 and PD-L1 belong to the B7 family co-stimulatory molecules fine-tuning the immune response. The present work investigates the clinical effect of B7-H6 protein expression with PD-L1 status and the infiltration of natural killer cells as potential biomarkers in breast tumor inflammatory microenvironment. The expression levels of B7-H6 protein by cancer cells and immune infiltrating cells in human breast cancer tissues and evaluate their associations with PD-L1 expression, NK cell status, clinical pathological features and prognosis were explored. The immunohistochemistry labeling method was used to assess B7-H6 and PD-L1 proteins expression by cancer and immune cells. The associations between immune checkpoint, major clinical pathological variables and survival rates were analyzed. B7-H6 protein was depicted in both breast and immune cells. Results showed that Tumor B7-H6 expression is highly associated with Her-2 over expression. B7-H6 + immune cells are highly related to the Scarff–Bloom–Richardson grade and associated with PD-L1 expression and NK cells status. Survival analysis revealed a better prognosis in patients with low expression of B7-H6 by cancer cells. Conversely, B7-H6 + immune cells were significantly associated with longer survival. Findings strongly suggest an interaction between B7 molecules that contributes to a particular design of the inflammatory microenvironment. This may influence the efficiency of therapies based on antibodies blocking the PD-L1/PD1 pathway and can explain the detection of clinical benefits only in a fraction of patients treated with immune checkpoint inhibitors.
format article
author Boutheina Cherif
Hana Triki
Slim Charfi
Lobna Bouzidi
Wala Ben Kridis
Afef Khanfir
Kais Chaabane
Tahya Sellami-Boudawara
Ahmed Rebai
author_facet Boutheina Cherif
Hana Triki
Slim Charfi
Lobna Bouzidi
Wala Ben Kridis
Afef Khanfir
Kais Chaabane
Tahya Sellami-Boudawara
Ahmed Rebai
author_sort Boutheina Cherif
title Immune checkpoint molecules B7-H6 and PD-L1 co-pattern the tumor inflammatory microenvironment in human breast cancer
title_short Immune checkpoint molecules B7-H6 and PD-L1 co-pattern the tumor inflammatory microenvironment in human breast cancer
title_full Immune checkpoint molecules B7-H6 and PD-L1 co-pattern the tumor inflammatory microenvironment in human breast cancer
title_fullStr Immune checkpoint molecules B7-H6 and PD-L1 co-pattern the tumor inflammatory microenvironment in human breast cancer
title_full_unstemmed Immune checkpoint molecules B7-H6 and PD-L1 co-pattern the tumor inflammatory microenvironment in human breast cancer
title_sort immune checkpoint molecules b7-h6 and pd-l1 co-pattern the tumor inflammatory microenvironment in human breast cancer
publisher Nature Portfolio
publishDate 2021
url https://doaj.org/article/e0f66d5c1c884bce981019b3b9ea42ee
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