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

Li, X.; Gruosso, T.; Zuo, D.; Omeroglu, A.; Meterissian, S.; Guiot, M.-C.; Salazar, A.; Park, M.; Levine, H.

doi:10.1101/430413

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bioRxiv · 10.1101/430413

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

Li, X.·Gruosso, T.·Zuo, D.·Omeroglu, A.·Meterissian, S.·Guiot, M.-C.·Salazar, A.·Park, M.·Levine, H.

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Abstract

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 tumorcell clusters in the core and margin regions in TNBC. Combining mathematical 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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Li, X., Gruosso, T., Zuo, D., Omeroglu, A., Meterissian, S., Guiot, M.-C., Salazar, A., Park, M., Levine, H.. 2018-10-02. Infiltration of CD8+ T cells into tumor-cell clusters in Triple Negative Breast Cancer. https://doi.org/10.1101/430413

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