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B cell immune profiles in dysbiotic vermiform appendixes of pancreatic cancer patients

Pancreatic ductal adenocarcinoma (PDAC) remains one of the deadliest solid tumors and is resistant to immunotherapy. B cells play an essential role in PDAC progression and immune responses, both locally and systemically. Moreover, increasing evidence suggests that microbial compositions inside the t...

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Autores principales: Vietsch, Eveline E., Latifi, Diba, Verheij, Maaike, van der Oost, Elise W.A., de Wilde, Roeland F., Haen, Roel, van den Boom, Anne Loes, Koerkamp, Bas Groot, Doornebosch, Pascal G., van Verschuer, Victorien M.T., Ooms, Ariadne H.A.G., Mohammad, Farzana, Willemsen, Marcella, Aerts, Joachim G.J.V., Krog, Ricki T., de Miranda, Noel F.C.C., van den Bosch, Thierry P.P., Mueller, Yvonne M., Katsikis, Peter D., van Eijck, Casper H.J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10667699/
https://www.ncbi.nlm.nih.gov/pubmed/38022530
http://dx.doi.org/10.3389/fimmu.2023.1230306
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author Vietsch, Eveline E.
Latifi, Diba
Verheij, Maaike
van der Oost, Elise W.A.
de Wilde, Roeland F.
Haen, Roel
van den Boom, Anne Loes
Koerkamp, Bas Groot
Doornebosch, Pascal G.
van Verschuer, Victorien M.T.
Ooms, Ariadne H.A.G.
Mohammad, Farzana
Willemsen, Marcella
Aerts, Joachim G.J.V.
Krog, Ricki T.
de Miranda, Noel F.C.C.
van den Bosch, Thierry P.P.
Mueller, Yvonne M.
Katsikis, Peter D.
van Eijck, Casper H.J.
author_facet Vietsch, Eveline E.
Latifi, Diba
Verheij, Maaike
van der Oost, Elise W.A.
de Wilde, Roeland F.
Haen, Roel
van den Boom, Anne Loes
Koerkamp, Bas Groot
Doornebosch, Pascal G.
van Verschuer, Victorien M.T.
Ooms, Ariadne H.A.G.
Mohammad, Farzana
Willemsen, Marcella
Aerts, Joachim G.J.V.
Krog, Ricki T.
de Miranda, Noel F.C.C.
van den Bosch, Thierry P.P.
Mueller, Yvonne M.
Katsikis, Peter D.
van Eijck, Casper H.J.
author_sort Vietsch, Eveline E.
collection PubMed
description Pancreatic ductal adenocarcinoma (PDAC) remains one of the deadliest solid tumors and is resistant to immunotherapy. B cells play an essential role in PDAC progression and immune responses, both locally and systemically. Moreover, increasing evidence suggests that microbial compositions inside the tumor, as well as in the oral cavity and the gut, are important factors in shaping the PDAC immune landscape. However, the gut-associated lymphoid tissue (GALT) has not previously been explored in PDAC patients. In this study, we analyzed healthy vermiform appendix (VA) from 20 patients with PDAC and 32 patients with colon diseases by gene expression immune profiling, flow cytometry analysis, and microbiome sequencing. We show that the VA GALT of PDAC patients exhibits markers of increased inflammation and cytotoxic cell activity. In contrast, B cell function is decreased in PDAC VA GALT based on gene expression profiling; B cells express significantly fewer MHC class II surface receptors, whereas plasma cells express the immune checkpoint molecule HLA-G. Additionally, the vermiform appendix microbiome of PDAC patients is enriched with Klebsiella pneumoniae, Bifidobacterium animalis, and Adlercreutzia equolifaciens, while certain commensals are depleted. Our findings may suggest impaired B cell function within the GALT of PDAC patients, which could potentially be linked to microbial dysbiosis. Additional investigations are imperative to validate our observations and explore these potential targets of future therapies.
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spelling pubmed-106676992023-01-01 B cell immune profiles in dysbiotic vermiform appendixes of pancreatic cancer patients Vietsch, Eveline E. Latifi, Diba Verheij, Maaike van der Oost, Elise W.A. de Wilde, Roeland F. Haen, Roel van den Boom, Anne Loes Koerkamp, Bas Groot Doornebosch, Pascal G. van Verschuer, Victorien M.T. Ooms, Ariadne H.A.G. Mohammad, Farzana Willemsen, Marcella Aerts, Joachim G.J.V. Krog, Ricki T. de Miranda, Noel F.C.C. van den Bosch, Thierry P.P. Mueller, Yvonne M. Katsikis, Peter D. van Eijck, Casper H.J. Front Immunol Immunology Pancreatic ductal adenocarcinoma (PDAC) remains one of the deadliest solid tumors and is resistant to immunotherapy. B cells play an essential role in PDAC progression and immune responses, both locally and systemically. Moreover, increasing evidence suggests that microbial compositions inside the tumor, as well as in the oral cavity and the gut, are important factors in shaping the PDAC immune landscape. However, the gut-associated lymphoid tissue (GALT) has not previously been explored in PDAC patients. In this study, we analyzed healthy vermiform appendix (VA) from 20 patients with PDAC and 32 patients with colon diseases by gene expression immune profiling, flow cytometry analysis, and microbiome sequencing. We show that the VA GALT of PDAC patients exhibits markers of increased inflammation and cytotoxic cell activity. In contrast, B cell function is decreased in PDAC VA GALT based on gene expression profiling; B cells express significantly fewer MHC class II surface receptors, whereas plasma cells express the immune checkpoint molecule HLA-G. Additionally, the vermiform appendix microbiome of PDAC patients is enriched with Klebsiella pneumoniae, Bifidobacterium animalis, and Adlercreutzia equolifaciens, while certain commensals are depleted. Our findings may suggest impaired B cell function within the GALT of PDAC patients, which could potentially be linked to microbial dysbiosis. Additional investigations are imperative to validate our observations and explore these potential targets of future therapies. Frontiers Media S.A. 2023-11-10 /pmc/articles/PMC10667699/ /pubmed/38022530 http://dx.doi.org/10.3389/fimmu.2023.1230306 Text en Copyright © 2023 Vietsch, Latifi, Verheij, van der Oost, de Wilde, Haen, van den Boom, Koerkamp, Doornebosch, van Verschuer, Ooms, Mohammad, Willemsen, Aerts, Krog, de Miranda, van den Bosch, Mueller, Katsikis and van Eijck https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Immunology
Vietsch, Eveline E.
Latifi, Diba
Verheij, Maaike
van der Oost, Elise W.A.
de Wilde, Roeland F.
Haen, Roel
van den Boom, Anne Loes
Koerkamp, Bas Groot
Doornebosch, Pascal G.
van Verschuer, Victorien M.T.
Ooms, Ariadne H.A.G.
Mohammad, Farzana
Willemsen, Marcella
Aerts, Joachim G.J.V.
Krog, Ricki T.
de Miranda, Noel F.C.C.
van den Bosch, Thierry P.P.
Mueller, Yvonne M.
Katsikis, Peter D.
van Eijck, Casper H.J.
B cell immune profiles in dysbiotic vermiform appendixes of pancreatic cancer patients
title B cell immune profiles in dysbiotic vermiform appendixes of pancreatic cancer patients
title_full B cell immune profiles in dysbiotic vermiform appendixes of pancreatic cancer patients
title_fullStr B cell immune profiles in dysbiotic vermiform appendixes of pancreatic cancer patients
title_full_unstemmed B cell immune profiles in dysbiotic vermiform appendixes of pancreatic cancer patients
title_short B cell immune profiles in dysbiotic vermiform appendixes of pancreatic cancer patients
title_sort b cell immune profiles in dysbiotic vermiform appendixes of pancreatic cancer patients
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10667699/
https://www.ncbi.nlm.nih.gov/pubmed/38022530
http://dx.doi.org/10.3389/fimmu.2023.1230306
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