High Densities of Tumor-Associated Plasma Cells Predict Improved Prognosis in Triple Negative Breast Cancer
Breast cancer is the most common malignancy affecting women, but the heterogeneity of the condition is a significant obstacle to effective treatment. Triple negative breast cancers (TNBCs) do not express HER2 or the receptors for estrogen or progesterone, and so often have a poor prognosis. Tumor-in...
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Published in | Frontiers in immunology Vol. 9; p. 1209 |
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Main Authors | , , , , , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
Switzerland
Frontiers Media S.A
30.05.2018
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Subjects | |
Online Access | Get full text |
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Summary: | Breast cancer is the most common malignancy affecting women, but the heterogeneity of the condition is a significant obstacle to effective treatment. Triple negative breast cancers (TNBCs) do not express HER2 or the receptors for estrogen or progesterone, and so often have a poor prognosis. Tumor-infiltrating T cells have been well-characterized in TNBC, and increased numbers are associated with better outcomes; however, the potential roles of B cells and plasma cells have been large. Here, we conducted a retrospective correlative study on the expression of B cell/plasma cell-related genes, and the abundance and localization of B cells and plasma cells within TNBCs, and clinical outcome. We analyzed 269 TNBC samples and used immunohistochemistry to quantify tumor-infiltrating B cells and plasma cells, coupled with NanoString measurement of expression of immunoglobulin metagenes. Multivariate analysis revealed that patients bearing TNBCs with above-median densities of CD38
plasma cells had significantly better disease-free survival (DFS) (HR = 0.44; 95% CI 0.26-0.77;
= 0.004) but not overall survival (OS), after adjusting for the effects of known prognostic factors. In contrast, TNBCs with higher immunoglobulin gene expression exhibited improved prognosis (OS
= 0.029 and DFS
= 0.005). The presence of B cells and plasma cells was positively correlated (
< 0.0001,
= 0.558), while immunoglobulin gene IGKC, IGHM, and IGHG1 mRNA expression correlated specifically with the density of CD38
plasma cells (IGKC
< 0.0001,
= 0.647; IGHM
< 0.0001,
= 0.580; IGHG1
< 0.0001,
= 0.655). Interestingly, after adjusting the multivariate analysis for the effect of intratumoral CD38
plasma cell density, the expression levels of all three genes lost significant prognostic value, suggesting a biologically important role of plasma cells. Last but not least, the addition of intratumoral CD38
plasma cell density to clinicopathological features significantly increased the prognostic value for both DFS (ΔLRχ
= 17.28,
= 1.71E-08) and OS (ΔLRχ
= 10.03,
= 6.32E-08), compared to clinicopathological features alone. The best combination was achieved by integrating intratumoral CD38
plasma cell density and IGHG1 which conferred the best added prognostic value for DFS (ΔLRχ
= 27.38,
= 5.22E-10) and OS (ΔLRχ
= 21.29,
= 1.03E-08). Our results demonstrate that the role of plasma cells in TNBC warrants further study to elucidate the relationship between their infiltration of tumors and disease recurrence. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 Edited by: Petranel Theresa Ferrao, University of Melbourne, Australia Specialty section: This article was submitted to Cancer Immunity and Immunotherapy, a section of the journal Frontiers in Immunology Reviewed by: Pin Wu, Zhejiang University, China; Marleen Kok, Netherlands Cancer Institute (NKI), Netherlands |
ISSN: | 1664-3224 1664-3224 |
DOI: | 10.3389/fimmu.2018.01209 |