TY - JOUR
T1 - Host indoleamine 2,3-dioxygenase
T2 - Contribution to systemic acquired tumor tolerance
AU - Johnson, Theodore S.
AU - Munn, David H.
N1 - Funding Information:
This work was supported by the Department of Pediatrics, the Immunotherapy Center, and the Cancer Center at Georgia Health Sciences University.
Copyright:
Copyright 2013 Elsevier B.V., All rights reserved.
PY - 2012/8
Y1 - 2012/8
N2 - Indoleamine 2,3-dioxygenase (IDO) is a natural mechanism of creating acquired tolerance in a variety of physiological settings. This endogenous tolerogenic pathway has important functions in regulating the magnitude of immune responses in settings of infection, pregnancy, tissue transplantation, mucosal interfaces and others. Whether for angiogenesis, stromal formation or immunologic tolerance, tumors often rely on recruiting host mechanisms. IDO is one such potent endogenous mechanism that appears to be frequently hijacked by tumors to establish systemic immune tolerance to tumor antigens. IDO can be expressed by tumors themselves, but, in addition, its natural site of expression is the host immune cells recruited by the tumor (particularly dendritic cells and macrophages). Therapeutic strategies that target the IDO pathway have been shown to synergize with standard chemotherapy and experimental immunotherapies to break tumor-induced tolerance. When such strategies target IDO expressed in host cells, they may be able to disrupt tolerance without creating intrinsic tumor cell drug resistance.
AB - Indoleamine 2,3-dioxygenase (IDO) is a natural mechanism of creating acquired tolerance in a variety of physiological settings. This endogenous tolerogenic pathway has important functions in regulating the magnitude of immune responses in settings of infection, pregnancy, tissue transplantation, mucosal interfaces and others. Whether for angiogenesis, stromal formation or immunologic tolerance, tumors often rely on recruiting host mechanisms. IDO is one such potent endogenous mechanism that appears to be frequently hijacked by tumors to establish systemic immune tolerance to tumor antigens. IDO can be expressed by tumors themselves, but, in addition, its natural site of expression is the host immune cells recruited by the tumor (particularly dendritic cells and macrophages). Therapeutic strategies that target the IDO pathway have been shown to synergize with standard chemotherapy and experimental immunotherapies to break tumor-induced tolerance. When such strategies target IDO expressed in host cells, they may be able to disrupt tolerance without creating intrinsic tumor cell drug resistance.
KW - Dioxygenase
KW - Host
KW - IDO
KW - Indoleamine
KW - Indoleamine 2,3-dioxygenase
KW - Tolerance
KW - Treg
KW - Tumor
UR - http://www.scopus.com/inward/record.url?scp=84866948348&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84866948348&partnerID=8YFLogxK
U2 - 10.3109/08820139.2012.689405
DO - 10.3109/08820139.2012.689405
M3 - Article
C2 - 23017145
AN - SCOPUS:84866948348
SN - 0882-0139
VL - 41
SP - 765
EP - 797
JO - Immunological Investigations
JF - Immunological Investigations
IS - 6-7
ER -