PMID- 37456260
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20230718
IS  - 2234-943X (Print)
IS  - 2234-943X (Electronic)
IS  - 2234-943X (Linking)
VI  - 13
DP  - 2023
TI  - The immunomodulatory role of IDO1-Kynurenine-NAD(+) pathway in switching cold 
      tumor microenvironment in PDAC.
PG  - 1142838
LID - 10.3389/fonc.2023.1142838 [doi]
LID - 1142838
AB  - Pancreatic ductal adenocarcinoma (PDAC) is the most common exocrine tumor of the 
      pancreas characterized by late diagnosis, adverse overall 5-year survival, a 
      higher propensity for metastatic disease, and lack of efficacy of systemic 
      therapy options. These adverse outcomes can be partly attributed to complex tumor 
      microenvironment (TME). Over the past decade, immunotherapy has revolutionized 
      the management of certain cancers; thus far, the immunologically 'non-inflamed' 
      tumor microenvironment in PDACs has proven to be challenging. Indolamine 
      2,3-dioxygenase 1 (IDO1) is the rate-limiting enzyme in the catabolic pathway of 
      L-Tryptophan, an essential amino acid, that gives rise to the immunosuppressive 
      metabolite Kynurenine. IDO1, Indolamine 2,3-dioxygenase 2 (IDO2), and Tryptophan 
      2,3-dioxygenase (TDO) are the key enzymes in the tryptophan catabolic pathway but 
      we focus on the role of the predominant enzyme form IDO1 in this review. 
      Nicotinamide phosphoribosyl transferase (iNAMPT) regulates the intracellular 
      concentration of NAD and is upregulated in the tumor. In light of the potential 
      role of IDO1 as a driver of hostile TME in PDAC and NAD(+) as a key coenzyme in 
      anti-tumor immune response, this review urges focus on extensive research and 
      initiation of clinical trials using IDO1 and NAMPT inhibitors in pancreatic 
      cancer in the future.
CI  - Copyright (c) 2023 Anu, Shiu and Khan.
FAU - Anu, R I
AU  - Anu RI
AD  - Department of Cancer Biology and Therapeutics, Precision Oncology and Multi-Omics 
      Clinic, Genetic Counseling Clinic, Department of Clinical Biochemistry, MVR 
      Cancer Centre and Research Institute, Calicut, Kerala, India.
FAU - Shiu, Kai-Keen
AU  - Shiu KK
AD  - Gastrointestinal Oncology Service, University College London Hospitals National 
      Health Services (NHS) Foundation Trust, London, United Kingdom.
AD  - Universtiy College London (UCL) Cancer Institute, University College London 
      Hospitals National Health Services (NHS) Foundation Trust, London, United 
      Kingdom.
FAU - Khan, Khurum Hayat
AU  - Khan KH
AD  - Gastrointestinal Oncology Service, University College London Hospitals National 
      Health Services (NHS) Foundation Trust, London, United Kingdom.
AD  - Universtiy College London (UCL) Cancer Institute, University College London 
      Hospitals National Health Services (NHS) Foundation Trust, London, United 
      Kingdom.
AD  - Whittington Health, National Health Services (NHS), London, United Kingdom.
LA  - eng
PT  - Journal Article
PT  - Review
DEP - 20230630
PL  - Switzerland
TA  - Front Oncol
JT  - Frontiers in oncology
JID - 101568867
PMC - PMC10348419
OTO - NOTNLM
OT  - Indolamine 2,3-dioxygenase 1
OT  - Kynurenine
OT  - NAD
OT  - NAMPT inhibitor
OT  - epacadostat
OT  - immune microenvironment
OT  - metabolome
OT  - pancreatic cancer
COIS- The authors declare that the research was conducted in the absence of any 
      commercial or financial relationships that could be construed as a potential 
      conflict of interest.
EDAT- 2023/07/17 06:42
MHDA- 2023/07/17 06:43
PMCR- 2023/01/01
CRDT- 2023/07/17 04:22
PHST- 2023/01/12 00:00 [received]
PHST- 2023/06/01 00:00 [accepted]
PHST- 2023/07/17 06:43 [medline]
PHST- 2023/07/17 06:42 [pubmed]
PHST- 2023/07/17 04:22 [entrez]
PHST- 2023/01/01 00:00 [pmc-release]
AID - 10.3389/fonc.2023.1142838 [doi]
PST - epublish
SO  - Front Oncol. 2023 Jun 30;13:1142838. doi: 10.3389/fonc.2023.1142838. eCollection 
      2023.