PMID- 34006522
OWN - NLM
STAT- MEDLINE
DCOM- 20220304
LR  - 20220304
IS  - 2326-6074 (Electronic)
IS  - 2326-6066 (Linking)
VI  - 9
IP  - 8
DP  - 2021 Aug
TI  - Arid5a Promotes Immune Evasion by Augmenting Tryptophan Metabolism and Chemokine 
      Expression.
PG  - 862-876
LID - 10.1158/2326-6066.CIR-21-0014 [doi]
AB  - The acquisition of mesenchymal traits leads to immune evasion in various cancers, 
      but the underlying molecular mechanisms remain unclear. In this study, we found 
      that the expression levels of AT-rich interaction domain-containing protein 5a 
      (Arid5a), an RNA-binding protein, were substantially increased in mesenchymal 
      tumor subtypes. The deletion of Arid5a in tumor cell lines enhanced antitumor 
      immunity in immunocompetent mice, but not in immunodeficient mice, suggesting a 
      role for Arid5a in immune evasion. Furthermore, an Arid5a-deficient tumor 
      microenvironment was shown to have robust antitumor immunity, as manifested by 
      suppressed infiltration of granulocytic myeloid-derived suppressor cells and 
      regulatory T cells. In addition, infiltrated T cells were more cytotoxic and less 
      exhausted. Mechanistically, Arid5a stabilized Ido1 and Ccl2 mRNAs and augmented 
      their expression, resulting in enhanced tryptophan catabolism and an 
      immunosuppressive tumor microenvironment. Thus, our findings demonstrate the role 
      of Arid5a beyond inflammatory diseases and suggest Arid5a as a promising target 
      for the treatment of immunotolerant malignant tumors.See related Spotlight by Van 
      den Eynde, p. 854.
CI  - (c)2021 American Association for Cancer Research.
FAU - Parajuli, Gyanu
AU  - Parajuli G
AUID- ORCID: 0000-0003-4674-1579
AD  - Laboratory of Immune Regulation, World Premier International Immunology Frontier 
      Research Center, Osaka University, Osaka, Japan.
FAU - Tekguc, Murat
AU  - Tekguc M
AUID- ORCID: 0000-0001-7570-5898
AD  - Experimental Immunology, World Premier International Immunology Frontier Research 
      Center, Osaka University, Osaka, Japan.
FAU - Wing, James B
AU  - Wing JB
AUID- ORCID: 0000-0002-3462-1003
AD  - Experimental Immunology, World Premier International Immunology Frontier Research 
      Center, Osaka University, Osaka, Japan.
FAU - Hashimoto, Ari
AU  - Hashimoto A
AD  - Department of Molecular Biology, Hokkaido University Graduate School of Medicine, 
      Sapporo, Japan.
FAU - Okuzaki, Daisuke
AU  - Okuzaki D
AUID- ORCID: 0000-0002-4552-783X
AD  - Genome Information Research Center, Research Institute for Microbial Diseases, 
      Osaka University, Osaka, Japan.
FAU - Hirata, Takeshi
AU  - Hirata T
AUID- ORCID: 0000-0002-0002-5190
AD  - Department of Molecular Neuroscience, Graduate School of Medicine/Graduate School 
      of Frontier Biosciences, Osaka University, Osaka, Japan.
AD  - Department of Neuro-Medical Science, Graduate School of Medicine, Osaka 
      University, Osaka, Japan.
AD  - Sohyaku, Innovative Research Division, Mitsubishi Tanabe Pharma Corporation, 
      Yokohama, Japan.
FAU - Sasaki, Atsushi
AU  - Sasaki A
AUID- ORCID: 0000-0002-5682-6480
AD  - Department of Molecular Neuroscience, Graduate School of Medicine/Graduate School 
      of Frontier Biosciences, Osaka University, Osaka, Japan.
AD  - Department of Neuro-Medical Science, Graduate School of Medicine, Osaka 
      University, Osaka, Japan.
AD  - Sohyaku, Innovative Research Division, Mitsubishi Tanabe Pharma Corporation, 
      Yokohama, Japan.
FAU - Itokazu, Takahide
AU  - Itokazu T
AUID- ORCID: 0000-0003-2977-7190
AD  - Department of Molecular Neuroscience, Graduate School of Medicine/Graduate School 
      of Frontier Biosciences, Osaka University, Osaka, Japan.
AD  - Department of Neuro-Medical Science, Graduate School of Medicine, Osaka 
      University, Osaka, Japan.
FAU - Handa, Haruka
AU  - Handa H
AUID- ORCID: 0000-0002-8557-7479
AD  - Department of Molecular Biology, Hokkaido University Graduate School of Medicine, 
      Sapporo, Japan.
FAU - Sugino, Hirokazu
AU  - Sugino H
AD  - Department of Cancer Pathology, Faculty of Medicine, Hokkaido University, 
      Sapporo, Japan.
FAU - Nishikawa, Yoshihiro
AU  - Nishikawa Y
AUID- ORCID: 0000-0002-1113-6937
AD  - Department of Gastroenterology and Hepatology, Kyoto University Graduate School 
      of Medicine, Kyoto, Japan.
FAU - Metwally, Hozaifa
AU  - Metwally H
AUID- ORCID: 0000-0002-8664-096X
AD  - Laboratory of Immune Regulation, World Premier International Immunology Frontier 
      Research Center, Osaka University, Osaka, Japan.
FAU - Kodama, Yuzo
AU  - Kodama Y
AUID- ORCID: 0000-0003-1223-7147
AD  - Department of Gastroenterology and Hepatology, Kyoto University Graduate School 
      of Medicine, Kyoto, Japan.
AD  - Division of Gastroenterology, Department of Internal Medicine, Kobe University 
      Graduate School of Medicine, Hyogo, Japan.
FAU - Tanaka, Shinya
AU  - Tanaka S
AD  - Department of Cancer Pathology, Faculty of Medicine, Hokkaido University, 
      Sapporo, Japan.
AD  - Institute for Chemical Reaction Design and Discovery (WPI-ICReDD), Hokkaido 
      University, Sapporo, Japan.
FAU - Sabe, Hisataka
AU  - Sabe H
AD  - Department of Molecular Biology, Hokkaido University Graduate School of Medicine, 
      Sapporo, Japan.
FAU - Yamashita, Toshihide
AU  - Yamashita T
AUID- ORCID: 0000-0003-4559-7018
AD  - Department of Molecular Neuroscience, Graduate School of Medicine/Graduate School 
      of Frontier Biosciences, Osaka University, Osaka, Japan.
AD  - Department of Neuro-Medical Science, Graduate School of Medicine, Osaka 
      University, Osaka, Japan.
FAU - Sakaguchi, Shimon
AU  - Sakaguchi S
AD  - Experimental Immunology, World Premier International Immunology Frontier Research 
      Center, Osaka University, Osaka, Japan.
FAU - Kishimoto, Tadamitsu
AU  - Kishimoto T
AD  - Laboratory of Immune Regulation, World Premier International Immunology Frontier 
      Research Center, Osaka University, Osaka, Japan. hashimot@ifrec.osaka-u.ac.jp 
      kishimoto@ifrec.osaka-u.ac.jp.
FAU - Hashimoto, Shigeru
AU  - Hashimoto S
AD  - Laboratory of Immune Regulation, World Premier International Immunology Frontier 
      Research Center, Osaka University, Osaka, Japan. hashimot@ifrec.osaka-u.ac.jp 
      kishimoto@ifrec.osaka-u.ac.jp.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20210518
PL  - United States
TA  - Cancer Immunol Res
JT  - Cancer immunology research
JID - 101614637
RN  - 0 (Arid5a protein, mouse)
RN  - 0 (Chemokines)
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (Transcription Factors)
RN  - 8DUH1N11BX (Tryptophan)
SB  - IM
CIN - Cancer Immunol Res. 2021 Aug;9(8):854. PMID: 34158281
MH  - Animals
MH  - Chemokines/*metabolism
MH  - DNA-Binding Proteins/*metabolism
MH  - Female
MH  - Humans
MH  - Immune Evasion/*immunology
MH  - Immunotherapy/*methods
MH  - Mice
MH  - Transcription Factors/*metabolism
MH  - Tryptophan/*metabolism
MH  - Xenograft Model Antitumor Assays
EDAT- 2021/05/20 06:00
MHDA- 2022/03/05 06:00
CRDT- 2021/05/19 05:50
PHST- 2021/01/14 00:00 [received]
PHST- 2021/03/05 00:00 [revised]
PHST- 2021/05/14 00:00 [accepted]
PHST- 2021/05/20 06:00 [pubmed]
PHST- 2022/03/05 06:00 [medline]
PHST- 2021/05/19 05:50 [entrez]
AID - 2326-6066.CIR-21-0014 [pii]
AID - 10.1158/2326-6066.CIR-21-0014 [doi]
PST - ppublish
SO  - Cancer Immunol Res. 2021 Aug;9(8):862-876. doi: 10.1158/2326-6066.CIR-21-0014. 
      Epub 2021 May 18.