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Infiltration of CD8+ T cells into tumor-cell clusters in Triple Negative Breast Cancer

By Xuefei Li, Tina Gruosso, Dongmei Zuo, Atilla Omeroglu, Sarkis Meterissian, Marie-Christine Guiot, Salazar Adam, Morag Park, Herbert Levine

Posted 02 Oct 2018
bioRxiv DOI: 10.1101/430413 (published DOI: 10.1073/pnas.1817652116)

Infiltration of CD8+ T lymphocytes into solid tumors is associated with good prognosis in various types of cancer, including Triple Negative Breast Cancers (TNBC). However, the mechanisms underlying different infiltration-levels are largely unknown. Here, we have characterized the spatial profile of CD8+ T cells around tumor-cell clusters in the core and margin regions in TNBC. Combining mathemati- cal modeling and data analysis, we propose that there exists a possible chemo-repellent inside tumor-cell clusters, which prevents CD8+ T cells from infiltrating into tumor-cell clusters. Furthermore, investigation into the properties of collagen fibers suggests that variations in desmoplastic elements does not limit infiltration of CD8+ T lymphocytes into tumor-cell clusters. This is consistent with the prediction of our mathematical modeling analysis whereby CD8+ T cells are predicted to infiltrate the fibrotic barrier and their infiltration into tumor clusters is governed by other mechanisms involving a local repellent.

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