Oncotarget

Research Papers:

Novel adherent CD11b+ Gr-1+ tumor-infiltrating cells initiate an immunosuppressive tumor microenvironment

Takuya Tsubaki, Tetsuya Kadonosono, Shimon Sakurai, Tadashi Shiozawa, Toshiki Goto, Shiori Sakai, Takahiro Kuchimaru, Takeharu Sakamoto, Hitomi Watanabe, Gen Kondoh and Shinae Kizaka-Kondoh _

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Oncotarget. 2018; 9:11209-11226. https://doi.org/10.18632/oncotarget.24359

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Abstract

Takuya Tsubaki1, Tetsuya Kadonosono1, Shimon Sakurai1, Tadashi Shiozawa1, Toshiki Goto1, Shiori Sakai1, Takahiro Kuchimaru1, Takeharu Sakamoto2, Hitomi Watanabe3, Gen Kondoh3 and Shinae Kizaka-Kondoh1

1School of Life Science and Technology, Tokyo Institute of Technology, Yokohama 226-8501, Japan

2Division of Molecular Pathology, Institute of Medical Science, The University of Tokyo, Minato-ku, Tokyo 108-8639, Japan

3Laboratory of Integrative Biological Science, Institute for Frontier Life and Medical Sciences, Kyoto University, Kyoto 606-8507, Japan

Correspondence to:

Shinae Kizaka-Kondoh, email: skondoh@bio.titech.ac.jp

Keywords: myeloid-derived suppressor cells; cancer microenvironment; tumor immunology; angiogenesis; tumor-associated macrophage

Received: November 11, 2017     Accepted: January 19, 2018     Published: January 29, 2018

ABSTRACT

The immunosuppressive tumor microenvironment is a hallmark of cancer. Myeloid-derived suppressor cells (MDSCs) are CD11b+ Gr-1+ tumor-infiltrating immature myeloid cells that strongly mediate tumor immunosuppression. The CD11b+ Gr-1+ cells are a heterogeneous cell population, and the impacts of each subpopulation on tumor progression are not yet completely understood. In the present study, we identified a novel subpopulation of CD11b+ Gr-1+ cells from murine lung carcinoma tumors according to their strongly adherent abilities. Although strong adherent activity is a unique property of macrophages, their marker expression patterns are similar to those of MDSCs; thus, we named this novel subpopulation MDSC-like adherent cells (MLACs). Unlike known MDSCs, MLACs lack the ability to suppress cytotoxic T lymphocytes and differentiate into tumor-associated macrophages (TAMs), but could still directly facilitate tumor growth and angiogenesis through secreting CCL2, CXCL1/2/5, PAI-1, MMPs, and VEGFA. Furthermore, MLACs recruited MDSCs via the secretion of CCL2/5 and CXCL1/2/5, thereby enhancing the immunosuppressive tumor microenvironment and promoting TAMs-mediated tumor progression. Our findings suggest that MLACs may function as an initiator of the immunosuppressive tumor microenvironment and highlight a new therapeutic target to prevent the onset or delay malignant progression.


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