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Loss of Lymphotoxin Alpha-Expressing Memory B Cells Correlates with Metastasis of Human Primary Melanoma

Activated antigen-experienced B cells play an unexpected complex role in anti-tumor immunity in human melanoma patients. However, correlative studies between B cell infiltration and tumor progression are limited by the lack of distinction between functional B cell subtypes. In this study, we examine...

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Autores principales: Werner, Franziska, Wagner, Christine, Simon, Martin, Glatz, Katharina, Mertz, Kirsten D., Läubli, Heinz, Richtig, Erika, Griss, Johannes, Wagner, Stephan N.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8307480/
https://www.ncbi.nlm.nih.gov/pubmed/34359321
http://dx.doi.org/10.3390/diagnostics11071238
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author Werner, Franziska
Wagner, Christine
Simon, Martin
Glatz, Katharina
Mertz, Kirsten D.
Läubli, Heinz
Richtig, Erika
Griss, Johannes
Wagner, Stephan N.
author_facet Werner, Franziska
Wagner, Christine
Simon, Martin
Glatz, Katharina
Mertz, Kirsten D.
Läubli, Heinz
Richtig, Erika
Griss, Johannes
Wagner, Stephan N.
author_sort Werner, Franziska
collection PubMed
description Activated antigen-experienced B cells play an unexpected complex role in anti-tumor immunity in human melanoma patients. However, correlative studies between B cell infiltration and tumor progression are limited by the lack of distinction between functional B cell subtypes. In this study, we examined a series of 59 primary and metastatic human cutaneous melanoma specimens with B cell infiltration. Using seven-color multiplex immunohistochemistry and automated tissue imaging and analysis, we analyzed the spatiotemporal dynamics of three major antigen-experienced B cell subpopulations expressing lymphotoxin alpha (LTA/TNFSF1) or interleukin-10 (IL-10) outside tertiary lymphoid structures. The expression of both LTA and IL-10 was not restricted to a particular B cell subtype. In primary melanomas, these cells were predominantly found at the invasive tumor-stroma front and, in metastatic melanomas, they were also found in the intratumoral stroma. In primary melanomas, decreased densities of LTA(+) memory-like and, to a lesser extent, activated B cells were associated with metastasis. Compared with metastatic primary tumors, B cell infiltrates in melanoma metastases were enriched in both LTA(+) memory-like and LTA(+) activated B cells, but not in any of the IL-10(+) B cell subpopulations. Melanoma disease progression shows distinct dynamics of functional B cell subpopulations, with the regulation of LTA(+) B cell numbers being more significant than IL-10(+) B cell subpopulations.
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spelling pubmed-83074802021-07-25 Loss of Lymphotoxin Alpha-Expressing Memory B Cells Correlates with Metastasis of Human Primary Melanoma Werner, Franziska Wagner, Christine Simon, Martin Glatz, Katharina Mertz, Kirsten D. Läubli, Heinz Richtig, Erika Griss, Johannes Wagner, Stephan N. Diagnostics (Basel) Article Activated antigen-experienced B cells play an unexpected complex role in anti-tumor immunity in human melanoma patients. However, correlative studies between B cell infiltration and tumor progression are limited by the lack of distinction between functional B cell subtypes. In this study, we examined a series of 59 primary and metastatic human cutaneous melanoma specimens with B cell infiltration. Using seven-color multiplex immunohistochemistry and automated tissue imaging and analysis, we analyzed the spatiotemporal dynamics of three major antigen-experienced B cell subpopulations expressing lymphotoxin alpha (LTA/TNFSF1) or interleukin-10 (IL-10) outside tertiary lymphoid structures. The expression of both LTA and IL-10 was not restricted to a particular B cell subtype. In primary melanomas, these cells were predominantly found at the invasive tumor-stroma front and, in metastatic melanomas, they were also found in the intratumoral stroma. In primary melanomas, decreased densities of LTA(+) memory-like and, to a lesser extent, activated B cells were associated with metastasis. Compared with metastatic primary tumors, B cell infiltrates in melanoma metastases were enriched in both LTA(+) memory-like and LTA(+) activated B cells, but not in any of the IL-10(+) B cell subpopulations. Melanoma disease progression shows distinct dynamics of functional B cell subpopulations, with the regulation of LTA(+) B cell numbers being more significant than IL-10(+) B cell subpopulations. MDPI 2021-07-12 /pmc/articles/PMC8307480/ /pubmed/34359321 http://dx.doi.org/10.3390/diagnostics11071238 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Werner, Franziska
Wagner, Christine
Simon, Martin
Glatz, Katharina
Mertz, Kirsten D.
Läubli, Heinz
Richtig, Erika
Griss, Johannes
Wagner, Stephan N.
Loss of Lymphotoxin Alpha-Expressing Memory B Cells Correlates with Metastasis of Human Primary Melanoma
title Loss of Lymphotoxin Alpha-Expressing Memory B Cells Correlates with Metastasis of Human Primary Melanoma
title_full Loss of Lymphotoxin Alpha-Expressing Memory B Cells Correlates with Metastasis of Human Primary Melanoma
title_fullStr Loss of Lymphotoxin Alpha-Expressing Memory B Cells Correlates with Metastasis of Human Primary Melanoma
title_full_unstemmed Loss of Lymphotoxin Alpha-Expressing Memory B Cells Correlates with Metastasis of Human Primary Melanoma
title_short Loss of Lymphotoxin Alpha-Expressing Memory B Cells Correlates with Metastasis of Human Primary Melanoma
title_sort loss of lymphotoxin alpha-expressing memory b cells correlates with metastasis of human primary melanoma
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8307480/
https://www.ncbi.nlm.nih.gov/pubmed/34359321
http://dx.doi.org/10.3390/diagnostics11071238
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