Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

T lymphocyte-derived IFN- facilitates breast cancer cells to pass the blood-brain barrier: an in vitro study corroborating translational data.

Rute M.S.M. Pedrosa
,
Johan M. Kros
* ORCID logo ,
Benjamin Schrijver
,
Cor Berrevoets
,
Rute B. Marques
,
Casper C.H.J. Van Eijck
ORCID logo ,
Reno Debets
,
Pieter J.M. Leenen
ORCID logo ,
Willem A. Dik
,
Dana A.M. Mustafa
ORCID logo
Version 1 : Received: 26 May 2023 / Approved: 29 May 2023 / Online: 29 May 2023 (08:24:41 CEST)

How to cite: Pedrosa, R.M.; Kros, J.M.; Schrijver, B.; Berrevoets, C.; Marques, R.B.; Van Eijck, C.C.; Debets, R.; Leenen, P.J.; Dik, W.A.; Mustafa, D.A. T lymphocyte-derived IFN- facilitates breast cancer cells to pass the blood-brain barrier: an in vitro study corroborating translational data.. Preprints 2023, 2023051994. https://doi.org/10.20944/preprints202305.1994.v1 Pedrosa, R.M.; Kros, J.M.; Schrijver, B.; Berrevoets, C.; Marques, R.B.; Van Eijck, C.C.; Debets, R.; Leenen, P.J.; Dik, W.A.; Mustafa, D.A. T lymphocyte-derived IFN- facilitates breast cancer cells to pass the blood-brain barrier: an in vitro study corroborating translational data.. Preprints 2023, 2023051994. https://doi.org/10.20944/preprints202305.1994.v1

Abstract

The appearance of brain metastasis is the most serious complication of breast cancer with mostly fatal outcomes. To reach the brain, tumor cells need to pass the blood-brain barrier (BBB). The molecular mechanisms underlying penetration of the BBB are largely unknown. Previously we found that tumor-infiltrating T lymphocytes enhance the development of brain metastasis of estrogen receptor-negative (ER-) breast cancer. In the current study, we investigate the contribution of T lymphocytes and the IFN- pathway in enabling breast cancer cells to pass the in vitro BBB. CD8+ cells display the strongest stimulatory effect on breast cancer cell passage. We show that inhibition of the IFN- receptor in MDA-MB-231 breast cancer cells, or neutralization of soluble IFN-, impairs the in vitro trespassing of breast cancer cells. Importantly, we validated our findings using gene expression data of breast cancer patients. CXCL-9,-10,-11/CXCR3 axis, dependent on IFN- signaling activity, was overexpressed in primary breast cancer samples of patients who developed brain metastasis. The data support a role for T-lymphocytes and the IFN- pathway in the formation of brain metastasis of ER- breast cancer, and offer targets to design future therapies for preventing breast cancer cells to cross the BBB.

Keywords

brain; metastasis; breast cancer; interferon-; blood-brain barrier; immune response; T lymphocytes

Subject

Biology and Life Sciences, Immunology and Microbiology

Copyright: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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