Inflammatory B cells correlate with failure to checkpoint blockade in melanoma patients

Kaat de Jonge; Laure Tillé; Joao Lourenco; Hélène Maby-El Hajjami; Sina Nassiri; Julien Racle; David Gfeller; Mauro Delorenzi; Grégory Verdeil; Petra Baumgaertner; Daniel E Speiser

doi:10.1080/2162402X.2021.1873585

Inflammatory B cells correlate with failure to checkpoint blockade in melanoma patients

Oncoimmunology. 2021 Feb 2;10(1):1873585. doi: 10.1080/2162402X.2021.1873585.

Authors

Kaat de Jonge¹, Laure Tillé¹, Joao Lourenco², Hélène Maby-El Hajjami¹, Sina Nassiri^{1

2}, Julien Racle^{3

4}, David Gfeller^{3

4}, Mauro Delorenzi², Grégory Verdeil¹, Petra Baumgaertner¹, Daniel E Speiser^{1

5}

Affiliations

¹ Department of Fundamental Oncology, University of Lausanne, Epalinges, Switzerland.
² Bioinformatics Core Facility, SIB Swiss Institute of Bioinformatics, Lausanne, Switzerland.
³ Department of Oncology, Ludwig Institute for Cancer Research, University of Lausanne, Lausanne, Switzerland.
⁴ SIB Swiss Institute of Bioinformatics, Lausanne, Switzerland.
⁵ Department of Oncology, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland.

Abstract

The understanding of the role of B cells in patients with solid tumors remains insufficient. We found that circulating B cells produced TNFα and/or IL-6, associated with unresponsiveness and poor overall survival of melanoma patients treated with anti-CTLA4 antibody. Transcriptome analysis of B cells from melanoma metastases showed enriched expression of inflammatory response genes. Publicly available single B cell data from the tumor microenvironment revealed a negative correlation between TNFα expression and response to immune checkpoint blockade. These findings suggest that B cells contribute to tumor growth via the production of inflammatory cytokines. Possibly, these B cells are different from tertiary lymphoid structure-associated B cells, which have been described to correlate with favorable clinical outcome of cancer patients. Further studies are required to identify and characterize B cell subsets and their functions promoting or counteracting tumor growth, with the aim to identify biomarkers and novel treatment targets.

Keywords: B cells; immune checkpoint; inflammation; melanoma; tumor microenvironment.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

B-Lymphocytes
Gene Expression Profiling
Humans
Melanoma* / drug therapy
Tertiary Lymphoid Structures*
Tumor Microenvironment

Grants and funding

This work was supported by the Swiss Cancer Research Foundation (KFS-3971-08-2016), Swiss TransMed (KIP 18), the Cancer Research Institute, Alfred and Annemarie von Sick and the University of Lausanne.