To better understand the phenotypes and development of myeloid-derived suppressor cells (MDSCs) in breast cancer, Alshetaiwi et al. sequenced RNA of single CD11b+Gr1+ splenocytes from wildtype or MMTV-PyMT mice. A conserved gene signature linked granulocytic (g) and monocytic MDSCs, was mirrored in human breast cancer, and revealed CD84 and JAML as specific MDSC surface markers. CD84hiCD11b+Gr1+ splenocytes displayed this signature, secreted ROS, and suppressed T cell proliferation in vitro. A pseudo-temporal analysis indicated that g-MDSCs may be derived from neutrophil progenitors in the spleen and not from circulating mature neutrophils.
Contributed by Alex Najibi
ABSTRACT: Myeloid-derived suppressor cells (MDSCs) are innate immune cells that acquire the capacity to suppress adaptive immune responses during cancer. It remains elusive how MDSCs differ from their normal myeloid counterparts, which limits our ability to specifically detect and therapeutically target MDSCs during cancer. Here, we sought to determine the molecular features of breast cancer-associated MDSCs using the widely studied mouse model based on the mouse mammary tumor virus (MMTV) promoter-driven expression of the polyomavirus middle T oncoprotein (MMTV-PyMT). To identify MDSCs in an unbiased manner, we used single-cell RNA sequencing to compare MDSC-containing splenic myeloid cells from breast tumor-bearing mice with wild-type controls. Our computational analysis of 14,646 single-cell transcriptomes revealed that MDSCs emerge through an aberrant neutrophil maturation trajectory in the spleen that confers them an immunosuppressive cell state. We establish the MDSC-specific gene signature and identify CD84 as a surface marker for improved detection and enrichment of MDSCs in breast cancers.
Author Info: (1) Department of Biological Chemistry, University of California, Irvine, Irvine, CA 92697, USA. Department of Pathology, University of Hail, Hail 2440, Saudi Arabia. (2) Center fo
Author Info: (1) Department of Biological Chemistry, University of California, Irvine, Irvine, CA 92697, USA. Department of Pathology, University of Hail, Hail 2440, Saudi Arabia. (2) Center for Complex Biological Systems, University of California, Irvine, Irvine, CA 92697, USA. (3) Department of Molecular Biology and Biochemistry, University of California, Irvine, Irvine, CA 92697, USA. (4) Department of Biological Chemistry, University of California, Irvine, Irvine, CA 92697, USA. (5) Department of Biological Chemistry, University of California, Irvine, Irvine, CA 92697, USA. (6) Ludwig Institute for Cancer Research, University of Lausanne, Epalinges 1066, Switzerland. (7) Department of Biological Chemistry, University of California, Irvine, Irvine, CA 92697, USA. (8) Department of Physiology and Biophysics, University of California, Irvine, Irvine, CA 92697, USA. (9) Department of Physiology and Biophysics, University of California, Irvine, Irvine, CA 92697, USA. (10) Department of Biological Chemistry, University of California, Irvine, Irvine, CA 92697, USA. (11) Department of Biological Chemistry, University of California, Irvine, Irvine, CA 92697, USA. (12) Department of Molecular Biology and Biochemistry, University of California, Irvine, Irvine, CA 92697, USA. (13) Department of Biological Chemistry, University of California, Irvine, Irvine, CA 92697, USA. kai.kessenbrock@uci.edu.
