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Review
. 2022 Jul;19(7):441-457.
doi: 10.1038/s41571-022-00619-z. Epub 2022 Apr 1.

B cells and tertiary lymphoid structures as determinants of tumour immune contexture and clinical outcome

Wolf H Fridman  1   2 , Maxime Meylan  3   4 , Florent Petitprez  5 , Cheng-Ming Sun  3   4 , Antoine Italiano  6   7 , Catherine Sautès-Fridman  3   4
Affiliations
Review

B cells and tertiary lymphoid structures as determinants of tumour immune contexture and clinical outcome

Wolf H Fridman et al. Nat Rev Clin Oncol. 2022 Jul.

Abstract

B cells are a major component of the tumour microenvironment, where they are predominantly associated with tertiary lymphoid structures (TLS). In germinal centres within mature TLS, B cell clones are selectively activated and amplified, and undergo antibody class switching and somatic hypermutation. Subsequently, these B cell clones differentiate into plasma cells that can produce IgG or IgA antibodies targeting tumour-associated antigens. In tumours without mature TLS, B cells are either scarce or differentiate into regulatory cells that produce immunosuppressive cytokines. Indeed, different tumours vary considerably in their TLS and B cell content. Notably, tumours with mature TLS, a high density of B cells and plasma cells, as well as the presence of antibodies to tumour-associated antigens are typically associated with favourable clinical outcomes and responses to immunotherapy compared with those lacking these characteristics. However, polyclonal B cell activation can also result in the formation of immune complexes that trigger the production of pro-inflammatory cytokines by macrophages and neutrophils. In complement-rich tumours, IgG antibodies can also activate the complement cascade, resulting in the production of anaphylatoxins that sustain tumour-promoting inflammation and angiogenesis. Herein, we review the phenotypic heterogeneity of intratumoural B cells and the importance of TLS in their generation as well as the potential of B cells and TLS as prognostic and predictive biomarkers. We also discuss novel therapeutic approaches that are being explored with the aim of increasing mature TLS formation, B cell differentiation and anti-tumour antibody production within tumours.

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