@article{a78d7f85dd1d468b98f4c316eb358283,
title = "Tetrathiomolybdate (TM)-associated copper depletion influences collagen remodeling and immune response in the pre-metastatic niche of breast cancer",
abstract = "Tetrathiomolybdate (TM) is a novel, copper-depleting compound associated with promising survival in a phase II study of patients with high-risk and triple-negative breast cancer. We sought to elucidate the mechanism of TM by exploring its effects on collagen processing and immune function in the tumor microenvironment (TME). Using an exploratory cohort, we identified markers of collagen processing (LOXL2, PRO-C3, C6M, and C1M) that differed between those with breast cancer versus controls. We measured these collagen biomarkers in TM-treated patients on the phase II study and detected evidence of decreased collagen cross-linking and increased degradation over formation in those without disease compared to those who experienced disease progression. Preclinical studies revealed decreased collagen deposition, lower levels of myeloid-derived suppressor cells, and higher CD4+ T-cell infiltration in TM-treated mice compared with controls. This study reveals novel mechanisms of TM targeting the TME and immune response with potential applications across cancer types.",
author = "Liu, {Ying L.} and Bager, {Cecilie Liv} and Nicholas Willumsen and Divya Ramchandani and Naomi Kornhauser and Lu Ling and Marta Cobham and Eleni Andreopoulou and Tessa Cigler and Anne Moore and Dayle LaPolla and Veronica Fitzpatrick and Maureen Ward and Warren, {J. David} and Claudia Fischbach and Vivek Mittal and Vahdat, {Linda T.}",
note = "Funding Information: We would like to thank the Breast Cancer Alliance of Greenwich, Komen Foundation, NY Community Trust, Cancer Research and Treatment, Anne Moore BC Research Fund, Stephen and Madeline Anbinder Foundation, Berman Fund, Keith Miller Foundation, Pisani Family Fund: Margy{\textquoteright}s Mission, Eric Lefkofsky, Anonymous Donor, Bay Ridge Subaru, “Share the Love” campaign, and TM patients and families. We would also like to thank Dr. Christopher Klebanoff (MSK) and Dr. Maureen Lane for helpful discussions. Collection of samples was partially supported by the National Center For Advancing Translational Sciences of the National Institutes of Health under Award Number UL1TR000457. Second Harmonic Generation Imaging was performed at Cornell University{\textquoteright}s Biotechnology Resource Center with funding from NYSTEM C029155 and Cornell{\textquoteright}s Center for the Physics of through Award Number 1U54CA210184 from the National Cancer Institute. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Publisher Copyright: {\textcopyright} 2021, The Author(s).",
year = "2021",
month = dec,
doi = "10.1038/s41523-021-00313-w",
language = "English (US)",
volume = "7",
journal = "npj Breast Cancer",
issn = "2374-4677",
publisher = "Nature Publishing Group",
number = "1",
}