PMID- 38369188
OWN - NLM
STAT- MEDLINE
DCOM- 20240422
LR  - 20240422
IS  - 1530-0285 (Electronic)
IS  - 0893-3952 (Linking)
VI  - 37
IP  - 4
DP  - 2024 Apr
TI  - Quantitative Multiplexed Analysis of Indoleamine 2,3-Dioxygenase (IDO) and 
      Arginase-1 (ARG1) Expression and Myeloid Cell Infiltration in Colorectal Cancer.
PG  - 100450
LID - S0893-3952(24)00030-9 [pii]
LID - 10.1016/j.modpat.2024.100450 [doi]
AB  - Indoleamine 2,3-dioxygenase (IDO) and arginase-1 (ARG1) are amino 
      acid-metabolizing enzymes, frequently highly expressed in cancer. Their 
      expression may deplete essential amino acids, lead to immunosuppression, and 
      promote cancer growth. Still, their expression patterns, prognostic significance, 
      and spatial localization in the colorectal cancer microenvironment are 
      incompletely understood. Using a custom 10-plex immunohistochemistry assay and 
      supervised machine learning-based digital image analysis, we characterized IDO 
      and ARG1 expression in monocytic cells, granulocytes, mast cells, and tumor cells 
      in 833 colorectal cancer patients. We evaluated the prognostic value and spatial 
      arrangement of IDO- and ARG1-expressing myeloid and tumor cells. IDO was mainly 
      expressed not only by monocytic cells but also by some tumor cells, whereas ARG1 
      was predominantly expressed by granulocytes. Higher density of IDO(+) monocytic 
      cells was an independent prognostic factor for improved cancer-specific survival 
      both in the tumor center (P(trend) = .0002; hazard ratio [HR] for the highest 
      ordinal category Q4 [vs Q1], 0.51; 95% CI, 0.33-0.79) and the invasive margin 
      (P(trend) = .0015). Higher density of granulocytes was associated with prolonged 
      cancer-specific survival in univariable models, and higher FCGR3(+)ARG1(+) 
      neutrophil density in the tumor center also in multivariable analysis (P(trend) = 
      .0020). Granulocytes were, on average, located closer to tumor cells than 
      monocytic cells. Furthermore, IDO(+) monocytic cells and ARG1(-) granulocytes 
      were closer than IDO(-) monocytic cells and ARG1(+) granulocytes, respectively. 
      The mRNA expression of the IDO1 gene was assessed in myeloid and tumor cells 
      using publicly available single-cell RNA sequencing data for 62 colorectal 
      cancers. IDO1 was mainly expressed in monocytes and dendritic cells, and high 
      IDO1 activity in monocytes was associated with enriched immunostimulatory 
      pathways. Our findings provided in-depth information about the infiltration 
      patterns and prognostic value of cells expressing IDO and/or ARG1 in the 
      colorectal cancer microenvironment, highlighting the significance of host immune 
      response in tumor progression.
CI  - Copyright (c) 2024 The Authors. Published by Elsevier Inc. All rights reserved.
FAU - Elomaa, Hanna
AU  - Elomaa H
AD  - Department of Biological and Environmental Science, University of Jyvaskyla, 
      Jyvaskyla, Finland; Department of Education and Research, Hospital Nova of 
      Central Finland, Well Being Services County of Central Finland, Jyvaskyla, 
      Finland.
FAU - Harkonen, Jouni
AU  - Harkonen J
AD  - Department of Pathology, Hospital Nova of Central Finland, Well Being Services 
      County of Central Finland, Jyvaskyla, Finland; Faculty of Health Sciences, A.I. 
      Virtanen Institute for Molecular Sciences, University of Eastern Finland, Kuopio, 
      Finland.
FAU - Vayrynen, Sara A
AU  - Vayrynen SA
AD  - Department of Internal Medicine, Oulu University Hospital, Oulu, Finland.
FAU - Ahtiainen, Maarit
AU  - Ahtiainen M
AD  - Department of Pathology, Hospital Nova of Central Finland, Well Being Services 
      County of Central Finland, Jyvaskyla, Finland.
FAU - Ogino, Shuji
AU  - Ogino S
AD  - Program in Molecular Pathological Epidemiology, Department of Pathology, Brigham 
      and Women's Hospital and Harvard Medical School, Boston, Massachusetts; 
      Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, 
      Massachusetts; Broad Institute of MIT and Harvard, Cambridge, Massachusetts; 
      Cancer Immunology and Cancer Epidemiology Programs, Dana-Farber Harvard Cancer 
      Center, Boston, Massachusetts.
FAU - Nowak, Jonathan A
AU  - Nowak JA
AD  - Program in Molecular Pathological Epidemiology, Department of Pathology, Brigham 
      and Women's Hospital and Harvard Medical School, Boston, Massachusetts.
FAU - Lau, Mai Chan
AU  - Lau MC
AD  - Bioinformatics Institute (BII), Agency of Science, Technology and Research 
      (A *STAR), Singapore, Singapore; Singapore Immunology Network (SIgN), Agency of 
      Science, Technology and Research (A *STAR), Singapore, Singapore.
FAU - Helminen, Olli
AU  - Helminen O
AD  - Translational Medicine Research Unit, Medical Research Center Oulu, Oulu 
      University Hospital, University of Oulu, Oulu, Finland.
FAU - Wirta, Erkki-Ville
AU  - Wirta EV
AD  - Department of Gastroenterology and Alimentary Tract Surgery, Tampere University 
      Hospital, Tampere, Finland; Faculty of Medicine and Health Technology, Tampere 
      University and Tays Cancer Center, Tampere University Hospital, Tampere, Finland.
FAU - Seppala, Toni T
AU  - Seppala TT
AD  - Faculty of Medicine and Health Technology, Tampere University and Tays Cancer 
      Center, Tampere University Hospital, Tampere, Finland; Department of 
      Gastrointestinal Surgery, Helsinki University Central Hospital, University of 
      Helsinki, Helsinki, Finland; Applied Tumor Genomics, Research Program Unit, 
      University of Helsinki, Helsinki, Finland; Abdominal Center, Helsinki University 
      Hospital, Helsinki, Finland.
FAU - Bohm, Jan
AU  - Bohm J
AD  - Department of Pathology, Hospital Nova of Central Finland, Well Being Services 
      County of Central Finland, Jyvaskyla, Finland.
FAU - Mecklin, Jukka-Pekka
AU  - Mecklin JP
AD  - Department of Education and Research, Hospital Nova of Central Finland, Well 
      Being Services County of Central Finland, Jyvaskyla, Finland; Faculty of Sport 
      and Health Sciences, University of Jyvaskyla, Jyvaskyla, Finland.
FAU - Kuopio, Teijo
AU  - Kuopio T
AD  - Department of Biological and Environmental Science, University of Jyvaskyla, 
      Jyvaskyla, Finland; Department of Pathology, Hospital Nova of Central Finland, 
      Well Being Services County of Central Finland, Jyvaskyla, Finland.
FAU - Vayrynen, Juha P
AU  - Vayrynen JP
AD  - Translational Medicine Research Unit, Medical Research Center Oulu, Oulu 
      University Hospital, University of Oulu, Oulu, Finland. Electronic address: 
      juha.vayrynen@oulu.fi.
LA  - eng
PT  - Journal Article
DEP - 20240216
PL  - United States
TA  - Mod Pathol
JT  - Modern pathology : an official journal of the United States and Canadian Academy 
      of Pathology, Inc
JID - 8806605
RN  - 0 (Indoleamine-Pyrrole 2,3,-Dioxygenase)
RN  - EC 3.5.3.1 (Arginase)
SB  - IM
MH  - Humans
MH  - *Indoleamine-Pyrrole 2,3,-Dioxygenase/metabolism
MH  - Arginase/metabolism
MH  - Prognosis
MH  - Myeloid Cells/metabolism
MH  - *Colorectal Neoplasms/genetics
MH  - Tumor Microenvironment
OTO - NOTNLM
OT  - bioimage analysis
OT  - colorectal carcinoma
OT  - multiplex immunohistochemistry
OT  - prognostic factors
OT  - spatial analysis
OT  - tumor immunology
EDAT- 2024/02/19 00:42
MHDA- 2024/04/22 06:45
CRDT- 2024/02/18 19:18
PHST- 2023/10/19 00:00 [received]
PHST- 2024/01/12 00:00 [revised]
PHST- 2024/02/04 00:00 [accepted]
PHST- 2024/04/22 06:45 [medline]
PHST- 2024/02/19 00:42 [pubmed]
PHST- 2024/02/18 19:18 [entrez]
AID - S0893-3952(24)00030-9 [pii]
AID - 10.1016/j.modpat.2024.100450 [doi]
PST - ppublish
SO  - Mod Pathol. 2024 Apr;37(4):100450. doi: 10.1016/j.modpat.2024.100450. Epub 2024 
      Feb 16.