A heparan-sulfate-bearing syndecan-1 glycoform is a distinct surface marker for intra-tumoral myeloid-derived suppressor cells
Thomas Welte,
Junhua Mai,
Zhe Zhang,
Shaohui Tian,
Guodong Zhang,
Yitian Xu,
Licheng Zhang,
Shu-shia Chen,
Tian Wang,
Haifa Shen
Affiliations
Thomas Welte
Department of Nanomedicine, Houston Methodist Academic Institute, Houston, TX 77030, USA
Junhua Mai
Department of Nanomedicine, Houston Methodist Academic Institute, Houston, TX 77030, USA
Zhe Zhang
Department of Nanomedicine, Houston Methodist Academic Institute, Houston, TX 77030, USA
Shaohui Tian
Department of Nanomedicine, Houston Methodist Academic Institute, Houston, TX 77030, USA
Guodong Zhang
Department of Nanomedicine, Houston Methodist Academic Institute, Houston, TX 77030, USA
Yitian Xu
Center for Immunotherapy Research, Houston Methodist Academic Institute, Houston, TX 77030, USA
Licheng Zhang
Center for Immunotherapy Research, Houston Methodist Academic Institute, Houston, TX 77030, USA
Shu-shia Chen
Center for Immunotherapy Research, Houston Methodist Academic Institute, Houston, TX 77030, USA
Tian Wang
Department of Microbiology & Immunology, The University of Texas Medical Branch, 301 University Boulevard, Galveston, TX 77555, USA
Haifa Shen
Department of Nanomedicine, Houston Methodist Academic Institute, Houston, TX 77030, USA; Innovative Therapeutic Program, Houston Methodist Cancer Center, Houston, TX 77030, USA; Department of Cell and Developmental Biology, Weill Cornell Medicine, New York, NY 10065, USA; Corresponding author
Summary: Myeloid-derived suppressor cells (MDSCs) infiltrate cancer tissue, promote tumor growth, and are associated with resistance to cancer therapies. However, there is no practical approach available to distinguish MDSCs from mature counterparts inside tumors. Here, we show that a recently isolated thioaptamer probe (T1) binds to MDSC subsets in colorectal and pancreatic tumors with high specificity. Whole transcriptome and functional analysis revealed that T1-binding cells contain polymorphonuclear (PMN)-MDSCs characterized by several immunosuppression pathways, ROS production, and T cell suppression activity, whereas T1-non-binding PMNs were mature and nonsuppressive. We identified syndecan-1 as the T1-interacting protein on MDSCs and chronic myelogenous leukemia K562 cell line. Heparan sulfate chains were essential in T1-binding. Inside tumors PMN-MDSCs expressed heparan sulfate biogenesis enzymes at higher levels. Tumor-cell-derived soluble factor(s) enhanced MDSCs' affinity for T1. Overall, we uncovered heparan-sulfate-dependent MDSC modulation in the tumor microenvironment and identified T1 as tool preferentially targeting tumor-promoting myeloid cell subsets.
