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Quantification of altered tissue turnover in a liquid biopsy: a proposed precision medicine tool to assess chronic inflammation and desmoplasia associated with a pro-cancerous niche and response to immuno-therapeutic anti-tumor modalities

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Abstract

Immuno-therapy has begun to revolutionize cancer treatment. However, despite the significant progress achieved in regard to the duration of clinical benefits, a substantial number of patients do not respond to these therapies. To improve the outcome of patients receiving immuno-therapy, there is a need for novel biomarkers that can predict and monitor treatment. Tumor microenvironment alterations, more specifically the state of chronic inflammation and desmoplasia (tumor fibrosis), are important factors to consider in this context. Here, we discuss the potential for quantification of altered tissue turnover in a liquid biopsy as a proposed precision medicine tool to assess chronic inflammation and desmoplasia in the immuno-oncology (IO) setting. We highlight the need for novel non-invasive biomarkers in IO and the importance of addressing tumor microenvironment alterations. We focus on desmoplasia and extracellular matrix (ECM) remodeling, and how the composition of the ECM defines T-cell permissiveness in the tumor microenvironment and opens up the possibility for associated liquid biopsy biomarkers. Moreover, we address the importance of the assessment of chronic inflammation, primarily macrophage activity, in a liquid biopsy.

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Abbreviations

ANGPT2:

Angiopoietin 2

AS:

Ankylosing spondylitis

BM:

Basement membrane

B-RAF:

Proto-oncogene B-Raf

CAF:

Cancer-associated fibroblast

CD:

Crohn’s disease

CDx:

Companion diagnostic

CTC:

Circulating tumor cell

ctDNA:

Circulating tumor DNA

Dt-GCT:

Diffuse-type giant cell tumor

ECM:

Extracellular matrix

FAK:

Focal adhesion kinase

FGFR:

Fibroblast growth factor receptor

GrzB:

Granzyme B

IO:

Immuno-oncology

IPF:

Idiopathic pulmonary fibrosis

LOX:

Lysyl oxidase

mCRC:

Metastatic colorectal cancer

miRNA:

MicroRNA

MMP:

Matrix metalloprotease

NSCLC:

Non-small cell lung cancer

PAD:

Peptidylarginine deiminase

PDAC:

Pancreas ductal adenocarcinoma

PRO-C3:

Pro-peptide of type III collagen formation

PTM:

Post-translational modification

RA:

Rheumatoid arthritis

SCLC:

Small cell lung cancer

SHH:

Sonic hedgehog

SRC:

Proto-oncogene tyrosine-protein kinase Src

TAM:

Tumor-associated macrophage

VEGFR:

Vascular endothelial growth factor receptor

VICM:

MMP-degraded and citrullinated vimentin

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  1. Nordic Bioscience, Biomarkers & Research, Herlev Hovedgade 205-207, Herlev, Denmark

    Nicholas Willumsen, Louise B. Thomsen, Cecilie L. Bager, Christina Jensen & Morten A. Karsdal

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  1. Nicholas Willumsen
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  2. Louise B. Thomsen
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  3. Cecilie L. Bager
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  4. Christina Jensen
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  5. Morten A. Karsdal
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Contributions

Conception of the work: NW and MK. Drafting the article: NW, LBT, and CJ. Preparing figures: CLB, NW, and LBT. Critical revision of the article: MK. Final approval: NW, LBT, CLB, CJ, and MAK.

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Correspondence to Nicholas Willumsen.

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Conflict of interest

All authors are employed at Nordic Bioscience involved in discovery and development of serological biomarkers.

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Willumsen, N., Thomsen, L.B., Bager, C.L. et al. Quantification of altered tissue turnover in a liquid biopsy: a proposed precision medicine tool to assess chronic inflammation and desmoplasia associated with a pro-cancerous niche and response to immuno-therapeutic anti-tumor modalities. Cancer Immunol Immunother 67, 1–12 (2018). https://doi.org/10.1007/s00262-017-2074-z

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  • DOI: https://doi.org/10.1007/s00262-017-2074-z

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