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Tertiary lymphoid structures and associated plasma cells play an important role in the biology of triple-negative breast cancers

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Abstract

Purpose

Triple-negative breast cancers (TNBC) are aggressive tumours that exhibit abundant lymphoid infiltrates which modulate tumour behaviour. Recent findings suggest that TNBC with higher densities of plasma cells are associated with a favourable prognosis, and tertiary lymphoid structures (TLS) have prognostic significance. Here, we studied the phenotype and function of plasma cells in TNBCs by assessing their association with IgG Kappa light chain expression, B cells, and TLS.

Methods

A retrospective analysis of 269 TNBC cases was performed. Tumour-infiltrating CD38+ plasma cells, CD20+ B cells, and TLS were evaluated on conventional haematoxylin–eosin-stained and immunohistochemical-stained sections of TNBC. We then selected TNBC cases demonstrating the highest and lowest densities of plasma cells, and examined their association with TLS, B cells, as well as immunoglobulin expression using Opal-Vectra multiplex immunofluorescence (IF).

Results

TNBC with high density of plasma cells showed significantly higher numbers of IgG Kappa+ CD38+ cells (p = 0.0089, p < 0.0001), and higher numbers of TLS (p < 0.0001), compared to TNBC with low density of plasma cells. TNBC with high density of plasma cells also showed higher numbers of CD20+ B cells in the tumour core (p < 0.0001), invasive margin (p < 0.0001), as well as stromal (p = 0.015) compartments.

Conclusion

TNBC with high density of plasma cells are associated with higher numbers of IgG Kappa+ CD38+ cells, CD20+ B cells, and TLS. Further studies to characterize the function of plasma cell infiltrates and how they may interact with other tumour-infiltrating lymphocytes and TLS in TNBC may help improve existing immunotherapy strategies.

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Authors and Affiliations

  1. Division of Pathology, Department of Anatomical Pathology, Singapore General Hospital, 20 College Road, Academia, Level 10, Singapore, 169856, Singapore

    Dominique Yuan Bin Seow, Joe Poh Sheng Yeong, Johnathan Xiande Lim, Jeffrey Chun Tatt Lim, Clara Chong Hui Ong, Puay Hoon Tan & Jabed Iqbal

  2. Department of Pathology, National University Hospital, 5, Lower Kent Ridge Road, 1 Main Building, Level 3, Singapore, 119074, Singapore

    Noel Chia

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  1. Dominique Yuan Bin Seow
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Seow, D.Y.B., Yeong, J.P.S., Lim, J.X. et al. Tertiary lymphoid structures and associated plasma cells play an important role in the biology of triple-negative breast cancers. Breast Cancer Res Treat 180, 369–377 (2020). https://doi.org/10.1007/s10549-020-05548-y

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