PMID- 32086381
OWN - NLM
STAT- MEDLINE
DCOM- 20201204
LR  - 20230502
IS  - 2470-9468 (Electronic)
IS  - 2470-9468 (Linking)
VI  - 5
IP  - 44
DP  - 2020 Feb 21
TI  - Defining the emergence of myeloid-derived suppressor cells in breast cancer using 
      single-cell transcriptomics.
LID - 10.1126/sciimmunol.aay6017 [doi]
LID - eaay6017
AB  - 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.
CI  - Copyright (c) 2020 The Authors, some rights reserved; exclusive licensee American 
      Association for the Advancement of Science. No claim to original U.S. Government 
      Works.
FAU - Alshetaiwi, Hamad
AU  - Alshetaiwi H
AUID- ORCID: 0000-0003-3144-7377
AD  - Department of Biological Chemistry, University of California, Irvine, Irvine, CA 
      92697, USA.
AD  - Department of Pathology, University of Hail, Hail 2440, Saudi Arabia.
FAU - Pervolarakis, Nicholas
AU  - Pervolarakis N
AUID- ORCID: 0000-0001-6210-4022
AD  - Center for Complex Biological Systems, University of California, Irvine, Irvine, 
      CA 92697, USA.
FAU - McIntyre, Laura Lynn
AU  - McIntyre LL
AUID- ORCID: 0000-0001-7820-4431
AD  - Department of Molecular Biology and Biochemistry, University of California, 
      Irvine, Irvine, CA 92697, USA.
FAU - Ma, Dennis
AU  - Ma D
AUID- ORCID: 0000-0002-3543-5560
AD  - Department of Biological Chemistry, University of California, Irvine, Irvine, CA 
      92697, USA.
FAU - Nguyen, Quy
AU  - Nguyen Q
AD  - Department of Biological Chemistry, University of California, Irvine, Irvine, CA 
      92697, USA.
FAU - Rath, Jan Akara
AU  - Rath JA
AD  - Ludwig Institute for Cancer Research, University of Lausanne, Epalinges 1066, 
      Switzerland.
FAU - Nee, Kevin
AU  - Nee K
AUID- ORCID: 0000-0002-9892-0598
AD  - Department of Biological Chemistry, University of California, Irvine, Irvine, CA 
      92697, USA.
FAU - Hernandez, Grace
AU  - Hernandez G
AUID- ORCID: 0000-0001-6494-6194
AD  - Department of Physiology and Biophysics, University of California, Irvine, 
      Irvine, CA 92697, USA.
FAU - Evans, Katrina
AU  - Evans K
AUID- ORCID: 0000-0002-1490-556X
AD  - Department of Physiology and Biophysics, University of California, Irvine, 
      Irvine, CA 92697, USA.
FAU - Torosian, Leona
AU  - Torosian L
AD  - Department of Biological Chemistry, University of California, Irvine, Irvine, CA 
      92697, USA.
FAU - Silva, Anushka
AU  - Silva A
AUID- ORCID: 0000-0002-7209-5032
AD  - Department of Biological Chemistry, University of California, Irvine, Irvine, CA 
      92697, USA.
FAU - Walsh, Craig
AU  - Walsh C
AD  - Department of Molecular Biology and Biochemistry, University of California, 
      Irvine, Irvine, CA 92697, USA.
FAU - Kessenbrock, Kai
AU  - Kessenbrock K
AUID- ORCID: 0000-0003-0410-6104
AD  - Department of Biological Chemistry, University of California, Irvine, Irvine, CA 
      92697, USA. kai.kessenbrock@uci.edu.
LA  - eng
GR  - R00 CA181490/CA/NCI NIH HHS/United States
GR  - R01 CA234496/CA/NCI NIH HHS/United States
GR  - U54 CA217378/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Sci Immunol
JT  - Science immunology
JID - 101688624
RN  - 0 (Biomarkers, Tumor)
RN  - 0 (CD84 protein, human)
RN  - 0 (Cd84 protein, mouse)
RN  - 0 (RNA, Neoplasm)
RN  - 0 (Signaling Lymphocytic Activation Molecule Family)
SB  - IM
MH  - Animals
MH  - Biomarkers, Tumor/genetics/immunology
MH  - Breast Neoplasms/immunology/*pathology
MH  - Cell Differentiation/genetics
MH  - Female
MH  - Humans
MH  - Mice
MH  - Mice, Inbred Strains
MH  - Mice, Transgenic
MH  - Myeloid-Derived Suppressor Cells/immunology/*pathology
MH  - RNA, Neoplasm/genetics/immunology
MH  - Signaling Lymphocytic Activation Molecule Family/genetics/immunology
MH  - *Single-Cell Analysis
MH  - *Transcriptome
PMC - PMC7219211
MID - NIHMS1582382
COIS- Competing interests: The authors declare no competing financial or non-financial 
      interests.
EDAT- 2020/02/23 06:00
MHDA- 2020/12/15 06:00
PMCR- 2020/08/21
CRDT- 2020/02/23 06:00
PHST- 2019/07/02 00:00 [received]
PHST- 2020/01/23 00:00 [accepted]
PHST- 2020/02/23 06:00 [entrez]
PHST- 2020/02/23 06:00 [pubmed]
PHST- 2020/12/15 06:00 [medline]
PHST- 2020/08/21 00:00 [pmc-release]
AID - 5/44/eaay6017 [pii]
AID - 10.1126/sciimmunol.aay6017 [doi]
PST - ppublish
SO  - Sci Immunol. 2020 Feb 21;5(44):eaay6017. doi: 10.1126/sciimmunol.aay6017.