Spatial distribution of B cells and lymphocyte clusters as a predictor of triple-negative breast cancer outcome

Abstract While tumor infiltration by CD8+ T cells is now widely accepted to predict outcomes, the clinical significance of intratumoral B cells is less clear. We hypothesized that spatial distribution rather than density of B cells within tumors may provide prognostic significance. We developed stat...

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Autores principales:	Juliana C. Wortman, Ting-Fang He, Shawn Solomon, Robert Z. Zhang, Anthony Rosario, Roger Wang, Travis Y. Tu, Daniel Schmolze, Yuan Yuan, Susan E. Yost, Xuefei Li, Herbert Levine, Gurinder Atwal, Peter P. Lee, Clare C. Yu
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
Acceso en línea:	https://doaj.org/article/fca31ce0d3c34634a8b3c1daa1c839e4
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spelling	oai:doaj.org-article:fca31ce0d3c34634a8b3c1daa1c839e42021-12-02T16:10:51ZSpatial distribution of B cells and lymphocyte clusters as a predictor of triple-negative breast cancer outcome10.1038/s41523-021-00291-z2374-4677https://doaj.org/article/fca31ce0d3c34634a8b3c1daa1c839e42021-07-01T00:00:00Zhttps://doi.org/10.1038/s41523-021-00291-zhttps://doaj.org/toc/2374-4677Abstract While tumor infiltration by CD8+ T cells is now widely accepted to predict outcomes, the clinical significance of intratumoral B cells is less clear. We hypothesized that spatial distribution rather than density of B cells within tumors may provide prognostic significance. We developed statistical techniques (fractal dimension differences and a box-counting method ‘occupancy’) to analyze the spatial distribution of tumor-infiltrating lymphocytes (TILs) in human triple-negative breast cancer (TNBC). Our results indicate that B cells in good outcome tumors (no recurrence within 5 years) are spatially dispersed, while B cells in poor outcome tumors (recurrence within 3 years) are more confined. While most TILs are located within the stroma, increased numbers of spatially dispersed lymphocytes within cancer cell islands are associated with a good prognosis. B cells and T cells often form lymphocyte clusters (LCs) identified via density-based clustering. LCs consist either of T cells only or heterotypic mixtures of B and T cells. Pure B cell LCs were negligible in number. Compared to tertiary lymphoid structures (TLS), LCs have fewer lymphocytes at lower densities. Both types of LCs are more abundant and more spatially dispersed in good outcomes compared to poor outcome tumors. Heterotypic LCs in good outcome tumors are smaller and more numerous compared to poor outcome. Heterotypic LCs are also closer to cancer islands in a good outcome, with LC size decreasing as they get closer to cancer cell islands. These results illuminate the significance of the spatial distribution of B cells and LCs within tumors.Juliana C. WortmanTing-Fang HeShawn SolomonRobert Z. ZhangAnthony RosarioRoger WangTravis Y. TuDaniel SchmolzeYuan YuanSusan E. YostXuefei LiHerbert LevineGurinder AtwalPeter P. LeeClare C. YuNature PortfolioarticleNeoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENnpj Breast Cancer, Vol 7, Iss 1, Pp 1-13 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
spellingShingle	Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Juliana C. Wortman Ting-Fang He Shawn Solomon Robert Z. Zhang Anthony Rosario Roger Wang Travis Y. Tu Daniel Schmolze Yuan Yuan Susan E. Yost Xuefei Li Herbert Levine Gurinder Atwal Peter P. Lee Clare C. Yu Spatial distribution of B cells and lymphocyte clusters as a predictor of triple-negative breast cancer outcome
description	Abstract While tumor infiltration by CD8+ T cells is now widely accepted to predict outcomes, the clinical significance of intratumoral B cells is less clear. We hypothesized that spatial distribution rather than density of B cells within tumors may provide prognostic significance. We developed statistical techniques (fractal dimension differences and a box-counting method ‘occupancy’) to analyze the spatial distribution of tumor-infiltrating lymphocytes (TILs) in human triple-negative breast cancer (TNBC). Our results indicate that B cells in good outcome tumors (no recurrence within 5 years) are spatially dispersed, while B cells in poor outcome tumors (recurrence within 3 years) are more confined. While most TILs are located within the stroma, increased numbers of spatially dispersed lymphocytes within cancer cell islands are associated with a good prognosis. B cells and T cells often form lymphocyte clusters (LCs) identified via density-based clustering. LCs consist either of T cells only or heterotypic mixtures of B and T cells. Pure B cell LCs were negligible in number. Compared to tertiary lymphoid structures (TLS), LCs have fewer lymphocytes at lower densities. Both types of LCs are more abundant and more spatially dispersed in good outcomes compared to poor outcome tumors. Heterotypic LCs in good outcome tumors are smaller and more numerous compared to poor outcome. Heterotypic LCs are also closer to cancer islands in a good outcome, with LC size decreasing as they get closer to cancer cell islands. These results illuminate the significance of the spatial distribution of B cells and LCs within tumors.
format	article
author	Juliana C. Wortman Ting-Fang He Shawn Solomon Robert Z. Zhang Anthony Rosario Roger Wang Travis Y. Tu Daniel Schmolze Yuan Yuan Susan E. Yost Xuefei Li Herbert Levine Gurinder Atwal Peter P. Lee Clare C. Yu
author_facet	Juliana C. Wortman Ting-Fang He Shawn Solomon Robert Z. Zhang Anthony Rosario Roger Wang Travis Y. Tu Daniel Schmolze Yuan Yuan Susan E. Yost Xuefei Li Herbert Levine Gurinder Atwal Peter P. Lee Clare C. Yu
author_sort	Juliana C. Wortman
title	Spatial distribution of B cells and lymphocyte clusters as a predictor of triple-negative breast cancer outcome
title_short	Spatial distribution of B cells and lymphocyte clusters as a predictor of triple-negative breast cancer outcome
title_full	Spatial distribution of B cells and lymphocyte clusters as a predictor of triple-negative breast cancer outcome
title_fullStr	Spatial distribution of B cells and lymphocyte clusters as a predictor of triple-negative breast cancer outcome
title_full_unstemmed	Spatial distribution of B cells and lymphocyte clusters as a predictor of triple-negative breast cancer outcome
title_sort	spatial distribution of b cells and lymphocyte clusters as a predictor of triple-negative breast cancer outcome
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/fca31ce0d3c34634a8b3c1daa1c839e4
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Spatial distribution of B cells and lymphocyte clusters as a predictor of triple-negative breast cancer outcome

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