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Transcriptomic analyses of myeloid-derived suppressor cell subsets in the circulation of colorectal cancer patients

Sasidharan Nair, V; Saleh, R; Toor, SM; Alajez, NM; Elkord, E

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Authors

V Sasidharan Nair

R Saleh

SM Toor

NM Alajez

E Elkord



Abstract

Myeloid-derived suppressor cells (MDSCs) promote tumor immune evasion and favor tumorigenesis by activating various tumor-promoting downstream signals. MDSC expansion is evident in the circulation and tumor microenvironment of many solid tumors including colorectal cancer (CRC). We have recently reported the transcriptomic profiles of tumor-infiltrating MDSCs in CRC patients and uncovered pathways, which could potentially assist tumor progression. In this study, we sorted different subsets of circulating MDSCs in CRC patients and investigated their transcriptomic profiles in order to disclose pathways, which could potentially contribute to disease progression. The sorted subsets included polymorphonuclear/granulocytic MDSCs (PMN-MDSCs), immature MDSCs (I-MDSCs), and monocytic MDSCs (M-MDSCs). Our functional annotation analyses revealed that multiple pathways including DNA damage-, chemotaxis-, apoptosis-, mitogen-activated protein kinase-, transforming growth factor β-, and myeloid differentiation–related transcripts were higher in PMN-MDSCs, compared with monocytic antigen-presenting cells (APCs) or I-MDSCs. Furthermore, genes related to Janus kinase (JAK)–signal transducer and activator of transcription (STAT) were also elevated in PMN-MDSCs. These data suggest that upregulation of JAK-STAT pathway could trigger multiple downstream targets in PMN-MDSCs, which favor tumor progression. Additionally, we found that pathways including phosphatidyl inositol 3-kinase (PI3K), interleukin 6, and TGF-β in M-MDSCs and cell cycle–related pathways in I-MDSCs were upregulated, compared with monocytic APCs. Moreover, acetylation-related genes were upregulated in both PMN-MDSCs and M-MDSCs. This latter finding implicates that epigenetic modifications could also play a role in the regulation of multiple tumor-promoting genes in PMN-MDSCs and M-MDSCs. Taken together, this study reveals various signaling pathways, which regulate the function of MDSC subsets in the circulation of CRC patients. However, functional studies are warranted to support these findings.

Citation

Sasidharan Nair, V., Saleh, R., Toor, S., Alajez, N., & Elkord, E. (2020). Transcriptomic analyses of myeloid-derived suppressor cell subsets in the circulation of colorectal cancer patients. Frontiers in Oncology, 10, 1530. https://doi.org/10.3389/fonc.2020.01530

Journal Article Type Article
Acceptance Date Jul 16, 2020
Online Publication Date Sep 2, 2020
Publication Date Sep 2, 2020
Deposit Date Sep 16, 2020
Publicly Available Date Sep 16, 2020
Journal Frontiers in Oncology
Publisher Frontiers Media
Volume 10
Pages 1530
DOI https://doi.org/10.3389/fonc.2020.01530
Keywords Oncology, colorectal cancer, RNASeq, myeloid-derived suppressor cells, JAK/STAT, histone acetylation
Publisher URL https://doi.org/10.3389/fonc.2020.01530
Related Public URLs https://www.frontiersin.org/journals/451
Additional Information Additional Information : ** From Frontiers via Jisc Publications Router ** Licence for this article: http://creativecommons.org/licenses/by/4.0/ **Journal IDs: eissn 2234-943X **History: published_online 02-09-2020; accepted 16-07-2020; submitted 10-06-2020; collection 2020
Funders : Qatar Biomedical Research Institute, Qatar Foundation
Grant Number: VR04

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