A pan-cancer single-cell RNA-seq atlas of intratumoral B cells

Evelyn Fitzsimons¹, Danwen Qian², Andrei Enica³, Krupa Thakkar⁴, Marcellus Augustine⁵, Samuel Gamble⁶, James L Reading⁶, Kevin Litchfield⁷

Affiliations

¹ Tumor Immunogenomics and Immunosurveillance Laboratory, University College London Cancer Institute, Paul O'Gorman, Building, 72 Huntley Street, London WC1E 6BT, UK; Cancer Research UK Lung Cancer Centre of Excellence, University College London Cancer Institute, Paul O'Gorman, Building, 72 Huntley Street, London WC1E 6BT, UK; Pre-Cancer Immunology Laboratory, University College London Cancer Institute, Paul O'Gorman, Building, 72 Huntley Street, London WC1E 6BT, UK.
² Tumor Immunogenomics and Immunosurveillance Laboratory, University College London Cancer Institute, Paul O'Gorman, Building, 72 Huntley Street, London WC1E 6BT, UK; Cancer Research UK Lung Cancer Centre of Excellence, University College London Cancer Institute, Paul O'Gorman, Building, 72 Huntley Street, London WC1E 6BT, UK. Electronic address: d.qian@ucl.ac.uk.
³ Cancer Research UK Lung Cancer Centre of Excellence, University College London Cancer Institute, Paul O'Gorman, Building, 72 Huntley Street, London WC1E 6BT, UK; Pre-Cancer Immunology Laboratory, University College London Cancer Institute, Paul O'Gorman, Building, 72 Huntley Street, London WC1E 6BT, UK; University College London Centre for 3D Models of Health and Disease, Division of Surgery and Interventional Science, Charles Bell House, 43-45 Foley Street, London W1W 7TY, UK.
⁴ Tumor Immunogenomics and Immunosurveillance Laboratory, University College London Cancer Institute, Paul O'Gorman, Building, 72 Huntley Street, London WC1E 6BT, UK; Cancer Research UK Lung Cancer Centre of Excellence, University College London Cancer Institute, Paul O'Gorman, Building, 72 Huntley Street, London WC1E 6BT, UK.
⁵ Tumor Immunogenomics and Immunosurveillance Laboratory, University College London Cancer Institute, Paul O'Gorman, Building, 72 Huntley Street, London WC1E 6BT, UK; Cancer Research UK Lung Cancer Centre of Excellence, University College London Cancer Institute, Paul O'Gorman, Building, 72 Huntley Street, London WC1E 6BT, UK; Cancer Evolution and Genome Instability Laboratory, The Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK; Division of Medicine, University College London, London WC1E 6BT, UK.
⁶ Cancer Research UK Lung Cancer Centre of Excellence, University College London Cancer Institute, Paul O'Gorman, Building, 72 Huntley Street, London WC1E 6BT, UK; Pre-Cancer Immunology Laboratory, University College London Cancer Institute, Paul O'Gorman, Building, 72 Huntley Street, London WC1E 6BT, UK.
⁷ Tumor Immunogenomics and Immunosurveillance Laboratory, University College London Cancer Institute, Paul O'Gorman, Building, 72 Huntley Street, London WC1E 6BT, UK; Cancer Research UK Lung Cancer Centre of Excellence, University College London Cancer Institute, Paul O'Gorman, Building, 72 Huntley Street, London WC1E 6BT, UK. Electronic address: k.litchfield@ucl.ac.uk.

PMID: 39406187
DOI: 10.1016/j.ccell.2024.09.011

Free article

A pan-cancer single-cell RNA-seq atlas of intratumoral B cells

Evelyn Fitzsimons et al. Cancer Cell. 2024.

Free article

. 2024 Oct 14;42(10):1784-1797.e4.

doi: 10.1016/j.ccell.2024.09.011.

Authors

Evelyn Fitzsimons¹, Danwen Qian², Andrei Enica³, Krupa Thakkar⁴, Marcellus Augustine⁵, Samuel Gamble⁶, James L Reading⁶, Kevin Litchfield⁷

Affiliations

¹ Tumor Immunogenomics and Immunosurveillance Laboratory, University College London Cancer Institute, Paul O'Gorman, Building, 72 Huntley Street, London WC1E 6BT, UK; Cancer Research UK Lung Cancer Centre of Excellence, University College London Cancer Institute, Paul O'Gorman, Building, 72 Huntley Street, London WC1E 6BT, UK; Pre-Cancer Immunology Laboratory, University College London Cancer Institute, Paul O'Gorman, Building, 72 Huntley Street, London WC1E 6BT, UK.
² Tumor Immunogenomics and Immunosurveillance Laboratory, University College London Cancer Institute, Paul O'Gorman, Building, 72 Huntley Street, London WC1E 6BT, UK; Cancer Research UK Lung Cancer Centre of Excellence, University College London Cancer Institute, Paul O'Gorman, Building, 72 Huntley Street, London WC1E 6BT, UK. Electronic address: d.qian@ucl.ac.uk.
³ Cancer Research UK Lung Cancer Centre of Excellence, University College London Cancer Institute, Paul O'Gorman, Building, 72 Huntley Street, London WC1E 6BT, UK; Pre-Cancer Immunology Laboratory, University College London Cancer Institute, Paul O'Gorman, Building, 72 Huntley Street, London WC1E 6BT, UK; University College London Centre for 3D Models of Health and Disease, Division of Surgery and Interventional Science, Charles Bell House, 43-45 Foley Street, London W1W 7TY, UK.
⁴ Tumor Immunogenomics and Immunosurveillance Laboratory, University College London Cancer Institute, Paul O'Gorman, Building, 72 Huntley Street, London WC1E 6BT, UK; Cancer Research UK Lung Cancer Centre of Excellence, University College London Cancer Institute, Paul O'Gorman, Building, 72 Huntley Street, London WC1E 6BT, UK.
⁵ Tumor Immunogenomics and Immunosurveillance Laboratory, University College London Cancer Institute, Paul O'Gorman, Building, 72 Huntley Street, London WC1E 6BT, UK; Cancer Research UK Lung Cancer Centre of Excellence, University College London Cancer Institute, Paul O'Gorman, Building, 72 Huntley Street, London WC1E 6BT, UK; Cancer Evolution and Genome Instability Laboratory, The Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK; Division of Medicine, University College London, London WC1E 6BT, UK.
⁶ Cancer Research UK Lung Cancer Centre of Excellence, University College London Cancer Institute, Paul O'Gorman, Building, 72 Huntley Street, London WC1E 6BT, UK; Pre-Cancer Immunology Laboratory, University College London Cancer Institute, Paul O'Gorman, Building, 72 Huntley Street, London WC1E 6BT, UK.
⁷ Tumor Immunogenomics and Immunosurveillance Laboratory, University College London Cancer Institute, Paul O'Gorman, Building, 72 Huntley Street, London WC1E 6BT, UK; Cancer Research UK Lung Cancer Centre of Excellence, University College London Cancer Institute, Paul O'Gorman, Building, 72 Huntley Street, London WC1E 6BT, UK. Electronic address: k.litchfield@ucl.ac.uk.

PMID: 39406187
DOI: 10.1016/j.ccell.2024.09.011

Abstract

Tumor-infiltrating B cells play a significant role in tumor development, progression, and prognosis, yet a comprehensive classification system is lacking. To address this gap, we present a pan-cancer single-cell RNA sequencing (scRNA-seq) atlas of tumor-infiltrating B and plasma cells across a large sample cohort. We identify key B cell subset signatures, revealing distinct subpopulations and highlighting the heterogeneity and functional diversity of these cells in the tumor microenvironment. We explore associations between B cell subsets and checkpoint inhibitor therapy responses, finding subset-specific effects on overall response. Additionally, we examine B and T cell crosstalk, identifying unique ligand-receptor pairs for specific B cell subsets, spatially validated. This comprehensive dataset serves as a valuable resource, providing a detailed atlas that enhances the understanding of B cell complexity in tumors and opens new avenues for research and therapeutic strategies.

Keywords: B cells; TME; atlas; cancer; checkpoint inhibitor therapy; single-cell RNA sequencing; spatial.

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Conflict of interest statement

Declaration of interests K.L. has the following disclosures (unrelated to this work): patent on indel burden and CPI response pending, patent on ctDNA minimal residual disease calling methods; speaker fees from Roche Tissue Diagnostics and Ellipses Pharma; research funding from CRUK TDL/Ono/LifeArc alliance and Genesis Therapeutics; and consulting roles with Monopteros Therapeutics, Kynos Therapeutics, SAGA Diagnostics, and Tempus Labs, Inc. Also unrelated to this work, K.L. is currently employed by Isomorphic Labs. J.L.R. has the following disclosures (unrelated to this work): patents filed for cancer early detection and consulting role for Achilles Therapeutics plc.

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A pan-cancer single-cell RNA-seq atlas of intratumoral B cells

Affiliations

A pan-cancer single-cell RNA-seq atlas of intratumoral B cells

Authors

Affiliations

Abstract

Conflict of interest statement

MeSH terms

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LinkOut - more resources

Full Text Sources

Medical

Miscellaneous