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

EE Vietsch, D Latifi, M Verheij, EWA van der Oost, RF de Wilde, R Haen, AL van den Boom, BG Koerkamp, PG Doornebosch, VMT van Verschuer, AHAG Ooms, F Mohammad, M Willemsen, JGJV Aerts, RT Krog, NFCC de Miranda, TPP van den Bosch, YM Mueller, PD Katsikis, CHJ van Eijck*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

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Abstract

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.

Original languageEnglish
Article number1230306
Number of pages15
JournalFrontiers in Immunology
Volume14
DOIs
Publication statusPublished - 10 Nov 2023

Bibliographical note

Publisher Copyright:
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.

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