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

• Published in: Diagnostics (Basel) Vol. 11; no. 7; p. 1238
• Main Authors: Werner, Franziska, Wagner, Christine, Simon, Martin, Glatz, Katharina, Mertz, Kirsten D., Läubli, Heinz, Richtig, Erika, Griss, Johannes, Wagner, Stephan N.
• Format: Journal Article
• Language: English
• Published: Basel MDPI AG 12.07.2021; MDPI
• Subjects: activated B cells; Antibodies; Antigens; Automation; Cloning; Cytokines; Dermatology; Ethics; human melanoma; Lymphatic system; Lymphocytes; lymphotoxin alpha; Melanoma; memory B cells; Metastasis; Pathology; tumor microenvironment; tumor-associated B cells; Tumors; United Kingdom > UK; United States > US
• ISSN: 2075-4418; 2075-4418
• DOI: 10.3390/diagnostics11071238

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.