Infiltration of CD8 + T cells into tumor cell clusters in triple-negative breast cancer.

Autor:	Li X; Center for Theoretical Biological Physics, Rice University, Houston, TX 77030., Gruosso T; Goodman Cancer Research Centre, McGill University, Montreal, QC H3A 1A3, Canada.; Department of Oncology, McGill University, Montreal, QC H4A 3T2, Canada., Zuo D; Goodman Cancer Research Centre, McGill University, Montreal, QC H3A 1A3, Canada., Omeroglu A; Department of Pathology, McGill University Health Centre, Montreal, QC H4A 3J1, Canada., Meterissian S; Department of Oncology, McGill University, Montreal, QC H4A 3T2, Canada.; Department of Surgery, McGill University Health Centre, Montreal, QC H4A 3J1, Canada., Guiot MC; Department of Pathology, McGill University Health Centre, Montreal, QC H4A 3J1, Canada.; Montreal Neurological Institute and Hospital, McGill University, Montreal, QC H3A 2B4, Canada., Salazar A; Center for Theoretical Biological Physics, Rice University, Houston, TX 77030., Park M; Goodman Cancer Research Centre, McGill University, Montreal, QC H3A 1A3, Canada; herbert.levine@rice.edu morag.park@mcgill.ca.; Department of Oncology, McGill University, Montreal, QC H4A 3T2, Canada.; Department of Biochemistry, McGill University, Montreal, QC H3A 1A3, Canada., Levine H; Center for Theoretical Biological Physics, Rice University, Houston, TX 77030; herbert.levine@rice.edu morag.park@mcgill.ca.; Department of Bioengineering, Rice University, Houston, TX 77030.; Department of Physics, Northeastern University, Boston, MA 02115.
Jazyk:	angličtina
Zdroj:	Proceedings of the National Academy of Sciences of the United States of America [Proc Natl Acad Sci U S A] 2019 Feb 26; Vol. 116 (9), pp. 3678-3687. Date of Electronic Publication: 2019 Feb 07.
DOI:	10.1073/pnas.1817652116
Abstrakt:	Infiltration of [Formula: see text] T lymphocytes into solid tumors is associated with good prognosis in various types of cancer, including triple-negative breast cancer (TNBC). However, the mechanisms underlying different infiltration levels are largely unknown. Here, we have characterized the spatial profile of [Formula: see text] T cells around tumor cell clusters (tightly connected tumor cells) in the core and margin regions in TNBC patient samples. We found that in some patients, the [Formula: see text] T cell density first decreases when moving in from the boundary of the tumor cell clusters and then rises again when approaching the center. To explain various infiltration profiles, we modeled the dynamics of T cell density via partial differential equations. We spatially modulated the diffusion/chemotactic coefficients of T cells (to mimic physical barriers) or introduced the localized secretion of a diffusing T cell chemorepellent. Combining the spatial-profile analysis and the modeling led to support for the second idea; i.e., there exists a possible chemorepellent inside tumor cell clusters, which prevents [Formula: see text] T cells from infiltrating into tumor cell clusters. This conclusion was consistent with an investigation into the properties of collagen fibers which suggested that variations in desmoplastic elements does not limit infiltration of [Formula: see text] T lymphocytes, as we did not observe significant correlations between the level of T cell infiltration and fiber properties. Our work provides evidence that [Formula: see text] T cells can cross typical fibrotic barriers and thus their infiltration into tumor clusters is governed by other mechanisms possibly involving a local repellent. Competing Interests: The authors declare no conflict of interest.
Databáze:	MEDLINE
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