PMID- 32470491
OWN - NLM
STAT- MEDLINE
DCOM- 20210112
LR  - 20211204
IS  - 1872-7980 (Electronic)
IS  - 0304-3835 (Linking)
VI  - 487
DP  - 2020 Sep 1
TI  - Hypoxia: Turning vessels into vassals of cancer immunotolerance.
PG  - 74-84
LID - S0304-3835(20)30269-X [pii]
LID - 10.1016/j.canlet.2020.05.015 [doi]
AB  - Hypoxia is a universal feature of solid cancers caused by a mismatch between 
      cellular oxygen supply and consumption. To meet the increased demand for oxygen, 
      hypoxic cancer cells (CCs) induce a multifaceted process known as angiogenesis, 
      wherein new vessels are formed by the sprouting of pre-existing ones. In addition 
      to providing oxygen for growth and an exit route for dissemination, angiogenic 
      vessels and factors are co-opted by CCs to enable the generation of an 
      immunotolerant, hypoxic tumor microenvironment, leading to therapeutic failure 
      and mortality. In this review, we discuss how hypoxia-inducible factors (HIFs), 
      the mechanistic target of rapamycin (mTOR), and the unfolded protein response 
      (UPR) control angiogenic factors serving both vascular and immunomodulatory 
      functions in the tumor microenvironment. Possible therapeutic strategies, wherein 
      targeting oxygen sensing might enhance anti-angiogenic and 
      immunologically-mediated anti-cancer responses, are suggested.
CI  - Copyright (c) 2020 The Authors. Published by Elsevier B.V. All rights reserved.
FAU - Schito, Luana
AU  - Schito L
AD  - UCD School of Medicine and UCD Conway Institute of Biomolecular and Biomedical 
      Research, University College Dublin, Belfield, Dublin 4, D04 C7X2, Ireland. 
      Electronic address: luana.schito@ucd.ie.
FAU - Rey, Sergio
AU  - Rey S
AD  - UCD School of Medicine and UCD Conway Institute of Biomolecular and Biomedical 
      Research, University College Dublin, Belfield, Dublin 4, D04 C7X2, Ireland. 
      Electronic address: sergio.rey@ucd.ie.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Review
DEP - 20200526
PL  - Ireland
TA  - Cancer Lett
JT  - Cancer letters
JID - 7600053
RN  - 0 (Basic Helix-Loop-Helix Transcription Factors)
RN  - 0 (Hypoxia-Inducible Factor 1, alpha Subunit)
RN  - EC 2.7.1.1 (MTOR protein, human)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
SB  - IM
MH  - Basic Helix-Loop-Helix Transcription Factors/genetics
MH  - Blood Vessels/growth & development/pathology
MH  - Gene Expression Regulation, Neoplastic/genetics
MH  - Gene Regulatory Networks/genetics/immunology
MH  - Humans
MH  - Hypoxia-Inducible Factor 1, alpha Subunit/*genetics
MH  - Neoplasms/*genetics/immunology/pathology
MH  - Neovascularization, Pathologic/genetics/immunology/pathology
MH  - TOR Serine-Threonine Kinases/*genetics
MH  - Tumor Hypoxia/genetics/immunology
MH  - Tumor Microenvironment/*genetics/immunology
MH  - Unfolded Protein Response/*genetics/immunology
OTO - NOTNLM
OT  - Angiogenesis
OT  - Cancer
OT  - HIF
OT  - Hypoxia
OT  - Hypoxia-inducible factors
OT  - Immunotherapy
OT  - Oxygen sensing
OT  - Targeted therapy
OT  - Tumor microenvironment
OT  - UPR
OT  - mTOR
COIS- Declaration of competing interest The authors declare that no conflicts of 
      interest exist.
EDAT- 2020/05/30 06:00
MHDA- 2021/01/13 06:00
CRDT- 2020/05/30 06:00
PHST- 2020/02/02 00:00 [received]
PHST- 2020/04/27 00:00 [revised]
PHST- 2020/05/12 00:00 [accepted]
PHST- 2020/05/30 06:00 [pubmed]
PHST- 2021/01/13 06:00 [medline]
PHST- 2020/05/30 06:00 [entrez]
AID - S0304-3835(20)30269-X [pii]
AID - 10.1016/j.canlet.2020.05.015 [doi]
PST - ppublish
SO  - Cancer Lett. 2020 Sep 1;487:74-84. doi: 10.1016/j.canlet.2020.05.015. Epub 2020 
      May 26.