PT  - JOURNAL ARTICLE
AU  - Xuefei Li
AU  - Tina Gruosso
AU  - Dongmei Zuo
AU  - Atilla Omeroglu
AU  - Sarkis Meterissian
AU  - Marie-Christine Guiot
AU  - Salazar Adam
AU  - Morag Park
AU  - Herbert Levine
TI  - Infiltration of CD8<sup>+</sup> T cells into tumor-cell clusters in Triple Negative Breast Cancer
AID  - 10.1101/430413
DP  - 2018 Jan 01
TA  - bioRxiv
PG  - 430413
4099  - http://biorxiv.org/content/early/2018/10/02/430413.short
4100  - http://biorxiv.org/content/early/2018/10/02/430413.full
AB  - 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.