ORIGINAL RESEARCH article
Front. Immunol.
Sec. B Cell Biology
Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1587088
FCRLs and atypical transcriptional pattern in tumor infiltrating B cells from lung and renal cancer
Provisionally accepted
Ekaterina A Bryushkova1,2
Evgenii V Shchoka2,3
Daniil K Lukyanov2,4Marina B Gikalo1,5Natalya Mushenkova1,6Konstantin K Laktionov7Alexey M Kazakov7Oybek A Khalmurzaev7
Vsevolod Matveev7
Dmitriy M Chudakov1,2,4,8,9
Ekaterina Serebrovskaya1,2*- 1Pirogov Russian National Research Medical University, Moscow, Russia
- 2Institute of Bioorganic Chemistry (RAS), Moscow, Moscow Oblast, Russia
- 3Moscow Institute of Physics and Technology, Dolgoprudny, Moscow Oblast, Russia
- 4Center for Molecular and Cellular Biology, Moscow, Russia
- 5Moscow City Oncology Hospital No. 62, Moscow, Moscow Oblast, Russia
- 6Unicorn Capital Partners, Moscow, Russia
- 7Russian Cancer Research Center NN Blokhin, Moscow, Moscow Oblast, Russia
- 8Central European Institute of Technology (CEITEC), Brno, Olomouc, Czechia
- 9Abu Dhabi Stem Cells Center (ADSCC), Abu Dhabi, United Arab Emirates
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Advances in high-dimensional flow cytometry and single-cell RNA sequencing (scRNA-seq) have enhanced our understanding of the heterogeneity of tumor-infiltrating B cells (TIBs). Subpopulations of TIBs exhibit diverse, sometimes opposing roles in tumor control, influenced by surface molecule, cytokine, and transcription factor expression. IgA and IgG expression in tumors have shown predictive value in melanoma and KRAS-mutated, but not KRAS wild-type, lung adenocarcinoma (LUAD).To investigate the functional differences between B cells producing these isotypes, we performed bulk transcriptome analysis of tumor-infiltrating surface-IgA+ (sIgA+) and sIgG+ memory B cells in LUAD. In LUAD, sIgA+ B cells overexpressed FCRL4, PDCD1, and RUNX2, suggesting an atypical chronically antigen-stimulated phenotype with features of exhaustion. Public scRNA-seq data revealed FCRL4-expressing TIBs as a distinct cluster with upregulation of genes involved in IFNγ and IFNα responses.sIgG+ B cells from LUAD overexpressed IL5RA, indicating a role for IL-5 in class-switch recombination to IgG. TCGA LUAD cohort analysis showed that the FCRL4/CD20 expression ratio correlates with lower survival, reinforcing FCRL4 as a marker of dysfunctional TIBs. Additionally, in renal cancer, high IGHA1/IGHG1 ratios were linked to worse survival. These findings suggest that the IgA/IgG ratio in tumors reflects not only the TME cytokine environment, but also functional differences in B cell populations, providing insights into their diverse roles in tumor progression.
Keywords: tumor infiltrating B cells, surface IgA, ling adenocarcinoma, FcRL4, RUNX2
Received: 03 Mar 2025; Accepted: 15 Jul 2025.
Copyright: © 2025 Bryushkova, Shchoka, Lukyanov, Gikalo, Mushenkova, Laktionov, Kazakov, Khalmurzaev, Matveev, Chudakov and Serebrovskaya. 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) or licensor 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.
* Correspondence: Ekaterina Serebrovskaya, Pirogov Russian National Research Medical University, Moscow, Russia
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