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

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dc.citation.articleNumber84en_US
dc.citation.journalTitlenpj Breast Canceren_US
dc.citation.volumeNumber7en_US
dc.contributor.authorWortman, Juliana C.en_US
dc.contributor.authorHe, Ting-Fangen_US
dc.contributor.authorSolomon, Shawnen_US
dc.contributor.authorZhang, Robert Z.en_US
dc.contributor.authorRosario, Anthonyen_US
dc.contributor.authorWang, Rogeren_US
dc.contributor.authorTu, Travis Y.en_US
dc.contributor.authorSchmolze, Danielen_US
dc.contributor.authorYuan, Yuanen_US
dc.contributor.authorYost, Susan E.en_US
dc.contributor.authorLi, Xuefeien_US
dc.contributor.authorLevine, Herberten_US
dc.contributor.authorAtwal, Gurinderen_US
dc.contributor.authorLee, Peter P.en_US
dc.contributor.authorYu, Clare C.en_US
dc.contributor.orgBioengineeringen_US
dc.contributor.orgCenter for Theoretical Biological Physicsen_US
dc.date.accessioned2021-07-15T21:23:53Zen_US
dc.date.available2021-07-15T21:23:53Zen_US
dc.date.issued2021en_US
dc.description.abstractWhile 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.en_US
dc.identifier.citationWortman, Juliana C., He, Ting-Fang, Solomon, Shawn, et al.. "Spatial distribution of B cells and lymphocyte clusters as a predictor of triple-negative breast cancer outcome." <i>npj Breast Cancer,</i> 7, (2021) Springer Nature: https://doi.org/10.1038/s41523-021-00291-z.en_US
dc.identifier.digitals41523-021-00291-zen_US
dc.identifier.doihttps://doi.org/10.1038/s41523-021-00291-zen_US
dc.identifier.urihttps://hdl.handle.net/1911/111028en_US
dc.language.isoengen_US
dc.publisherSpringer Natureen_US
dc.rightsThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder.en_US
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/en_US
dc.titleSpatial distribution of B cells and lymphocyte clusters as a predictor of triple-negative breast cancer outcomeen_US
dc.typeJournal articleen_US
dc.type.dcmiTexten_US
dc.type.publicationpublisher versionen_US
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