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Exploring the immune microenvironment in small bowel adenocarcinoma using digital image analysis

BACKGROUND: Small bowel adenocarcinoma (SBA) is a rare malignancy of the small intestine associated with late stage diagnosis and poor survival outcome. High expression of immune cells and immune checkpoint biomarkers especially programmed cell death ligand-1 (PD-L1) have been shown to significantly...

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Autores principales: Sidi, Fatima Abdullahi, Bingham, Victoria, McQuaid, Stephen, Craig, Stephanie G., Turkington, Richard C., James, Jacqueline A., Humphries, Matthew P., Salto-Tellez, Manuel
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10393147/
https://www.ncbi.nlm.nih.gov/pubmed/37527282
http://dx.doi.org/10.1371/journal.pone.0289355
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author Sidi, Fatima Abdullahi
Bingham, Victoria
McQuaid, Stephen
Craig, Stephanie G.
Turkington, Richard C.
James, Jacqueline A.
Humphries, Matthew P.
Salto-Tellez, Manuel
author_facet Sidi, Fatima Abdullahi
Bingham, Victoria
McQuaid, Stephen
Craig, Stephanie G.
Turkington, Richard C.
James, Jacqueline A.
Humphries, Matthew P.
Salto-Tellez, Manuel
author_sort Sidi, Fatima Abdullahi
collection PubMed
description BACKGROUND: Small bowel adenocarcinoma (SBA) is a rare malignancy of the small intestine associated with late stage diagnosis and poor survival outcome. High expression of immune cells and immune checkpoint biomarkers especially programmed cell death ligand-1 (PD-L1) have been shown to significantly impact disease progression. We have analysed the expression of a subset of immune cell and immune checkpoint biomarkers in a cohort of SBA patients and assessed their impact on progression-free survival (PFS) and overall survival (OS). METHODS: 25 patient samples in the form of formalin fixed, paraffin embedded (FFPE) tissue were obtained in tissue microarray (TMAs) format. Automated immunohistochemistry (IHC) staining was performed using validated antibodies for CD3, CD4, CD8, CD68, PD-L1, ICOS, IDO1 and LAG3. Slides were scanned digitally and assessed in QuPath, an open source image analysis software, for biomarker density and percentage positivity. Survival analyses were carried out using the Kaplan Meier method. RESULTS: Varying expressions of biomarkers were recorded. High expressions of CD3, CD4 and IDO1 were significant for PFS (p = 0.043, 0.020 and 0.018 respectively). High expression of ICOS was significant for both PFS (p = 0.040) and OS (p = 0.041), while high PD-L1 expression in tumour cells was significant for OS (p = 0.033). High correlation was observed between PD-L1 and IDO1 expressions (Pearson correlation co-efficient = 1) and subsequently high IDO1 expression in tumour cells was found to be significant for PFS (p = 0.006) and OS (p = 0.034). CONCLUSIONS: High levels of immune cells and immune checkpoint proteins have a significant impact on patient survival in SBA. These data could provide an insight into the immunotherapeutic management of patients with SBA.
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spelling pubmed-103931472023-08-02 Exploring the immune microenvironment in small bowel adenocarcinoma using digital image analysis Sidi, Fatima Abdullahi Bingham, Victoria McQuaid, Stephen Craig, Stephanie G. Turkington, Richard C. James, Jacqueline A. Humphries, Matthew P. Salto-Tellez, Manuel PLoS One Research Article BACKGROUND: Small bowel adenocarcinoma (SBA) is a rare malignancy of the small intestine associated with late stage diagnosis and poor survival outcome. High expression of immune cells and immune checkpoint biomarkers especially programmed cell death ligand-1 (PD-L1) have been shown to significantly impact disease progression. We have analysed the expression of a subset of immune cell and immune checkpoint biomarkers in a cohort of SBA patients and assessed their impact on progression-free survival (PFS) and overall survival (OS). METHODS: 25 patient samples in the form of formalin fixed, paraffin embedded (FFPE) tissue were obtained in tissue microarray (TMAs) format. Automated immunohistochemistry (IHC) staining was performed using validated antibodies for CD3, CD4, CD8, CD68, PD-L1, ICOS, IDO1 and LAG3. Slides were scanned digitally and assessed in QuPath, an open source image analysis software, for biomarker density and percentage positivity. Survival analyses were carried out using the Kaplan Meier method. RESULTS: Varying expressions of biomarkers were recorded. High expressions of CD3, CD4 and IDO1 were significant for PFS (p = 0.043, 0.020 and 0.018 respectively). High expression of ICOS was significant for both PFS (p = 0.040) and OS (p = 0.041), while high PD-L1 expression in tumour cells was significant for OS (p = 0.033). High correlation was observed between PD-L1 and IDO1 expressions (Pearson correlation co-efficient = 1) and subsequently high IDO1 expression in tumour cells was found to be significant for PFS (p = 0.006) and OS (p = 0.034). CONCLUSIONS: High levels of immune cells and immune checkpoint proteins have a significant impact on patient survival in SBA. These data could provide an insight into the immunotherapeutic management of patients with SBA. Public Library of Science 2023-08-01 /pmc/articles/PMC10393147/ /pubmed/37527282 http://dx.doi.org/10.1371/journal.pone.0289355 Text en © 2023 Sidi et al https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Sidi, Fatima Abdullahi
Bingham, Victoria
McQuaid, Stephen
Craig, Stephanie G.
Turkington, Richard C.
James, Jacqueline A.
Humphries, Matthew P.
Salto-Tellez, Manuel
Exploring the immune microenvironment in small bowel adenocarcinoma using digital image analysis
title Exploring the immune microenvironment in small bowel adenocarcinoma using digital image analysis
title_full Exploring the immune microenvironment in small bowel adenocarcinoma using digital image analysis
title_fullStr Exploring the immune microenvironment in small bowel adenocarcinoma using digital image analysis
title_full_unstemmed Exploring the immune microenvironment in small bowel adenocarcinoma using digital image analysis
title_short Exploring the immune microenvironment in small bowel adenocarcinoma using digital image analysis
title_sort exploring the immune microenvironment in small bowel adenocarcinoma using digital image analysis
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10393147/
https://www.ncbi.nlm.nih.gov/pubmed/37527282
http://dx.doi.org/10.1371/journal.pone.0289355
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