Chemo-immunotherapy: Role of indoleamine 2,3-dioxygenase in defining immunogenic versus tolerogenic cell death in the tumor microenvironment

Research output: Chapter in Book/Report/Conference proceedingChapter

8 Citations (Scopus)

Abstract

In certain settings, chemotherapy can trigger an immunogenic form of tumor cell death. More often, however, tumor cell death after chemotherapy is not immunogenic, and may be actively tolerizing. However, even in these settings the dying tumor cells may be much more immunogenic than previously recognized, if key suppressive immune checkpoints such as indoleamine 2,3-dioxygenase (IDO) can be blocked. This is an important question, because a robust immune response to dying tumor cells could potentially augment the efficacy of conventional chemotherapy, or enhance the strength and duration of response to other immunologic therapies. Recent findings using preclinical models of self-tolerance and autoimmunity suggest that IDO and related downstream pathways may play a fundamental role in the decision between tolerance versus immune activation in response to dying cells. Thus, in the period of tumor cell death following chemotherapy or immunotherapy, the presence of IDO may help dictate the choice between dominant immunosuppression versus inflammation, antigen cross-presentation, and epitope spreading. The IDO pathway thus differs from other checkpoint-blockade strategies, in that it affects early immune responses, at the level of inflammation, activation of antigen-presenting cells, and initial cross-presentation of tumor antigens. This “up-stream” position may make IDO a potent target for therapeutic inhibition.

Original languageEnglish (US)
Title of host publicationAdvances in Experimental Medicine and Biology
PublisherSpringer New York LLC
Pages91-104
Number of pages14
DOIs
StatePublished - Jan 1 2017

Publication series

NameAdvances in Experimental Medicine and Biology
Volume1036
ISSN (Print)0065-2598
ISSN (Electronic)2214-8019

Fingerprint

Indoleamine-Pyrrole 2,3,-Dioxygenase
Tumor Microenvironment
Cell death
Chemotherapy
Immunotherapy
Tumors
Cell Death
Cross-Priming
Drug Therapy
Neoplasms
Chemical activation
Cells
Inflammation
Self Tolerance
Immune Tolerance
Antigen Presentation
Neoplasm Antigens
Antigen-Presenting Cells
Autoimmunity
Immunosuppression

Keywords

  • Checkpoint
  • Chemotherapy
  • IDO
  • Immunotherapy
  • Indoleamine 2,3-dioxygenase
  • Radiation
  • Tolerance
  • Tumor
  • Tumor microenvironment

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Johnson, T. S., McGaha, T. L., & Munn, D. H. (2017). Chemo-immunotherapy: Role of indoleamine 2,3-dioxygenase in defining immunogenic versus tolerogenic cell death in the tumor microenvironment. In Advances in Experimental Medicine and Biology (pp. 91-104). (Advances in Experimental Medicine and Biology; Vol. 1036). Springer New York LLC. https://doi.org/10.1007/978-3-319-67577-0_7

Chemo-immunotherapy : Role of indoleamine 2,3-dioxygenase in defining immunogenic versus tolerogenic cell death in the tumor microenvironment. / Johnson, Theodore Samuel; McGaha, Tracy L.; Munn, David H.

Advances in Experimental Medicine and Biology. Springer New York LLC, 2017. p. 91-104 (Advances in Experimental Medicine and Biology; Vol. 1036).

Research output: Chapter in Book/Report/Conference proceedingChapter

Johnson, TS, McGaha, TL & Munn, DH 2017, Chemo-immunotherapy: Role of indoleamine 2,3-dioxygenase in defining immunogenic versus tolerogenic cell death in the tumor microenvironment. in Advances in Experimental Medicine and Biology. Advances in Experimental Medicine and Biology, vol. 1036, Springer New York LLC, pp. 91-104. https://doi.org/10.1007/978-3-319-67577-0_7
Johnson TS, McGaha TL, Munn DH. Chemo-immunotherapy: Role of indoleamine 2,3-dioxygenase in defining immunogenic versus tolerogenic cell death in the tumor microenvironment. In Advances in Experimental Medicine and Biology. Springer New York LLC. 2017. p. 91-104. (Advances in Experimental Medicine and Biology). https://doi.org/10.1007/978-3-319-67577-0_7
Johnson, Theodore Samuel ; McGaha, Tracy L. ; Munn, David H. / Chemo-immunotherapy : Role of indoleamine 2,3-dioxygenase in defining immunogenic versus tolerogenic cell death in the tumor microenvironment. Advances in Experimental Medicine and Biology. Springer New York LLC, 2017. pp. 91-104 (Advances in Experimental Medicine and Biology).
@inbook{68877a4633aa402a9ed4066aa0eef769,
title = "Chemo-immunotherapy: Role of indoleamine 2,3-dioxygenase in defining immunogenic versus tolerogenic cell death in the tumor microenvironment",
abstract = "In certain settings, chemotherapy can trigger an immunogenic form of tumor cell death. More often, however, tumor cell death after chemotherapy is not immunogenic, and may be actively tolerizing. However, even in these settings the dying tumor cells may be much more immunogenic than previously recognized, if key suppressive immune checkpoints such as indoleamine 2,3-dioxygenase (IDO) can be blocked. This is an important question, because a robust immune response to dying tumor cells could potentially augment the efficacy of conventional chemotherapy, or enhance the strength and duration of response to other immunologic therapies. Recent findings using preclinical models of self-tolerance and autoimmunity suggest that IDO and related downstream pathways may play a fundamental role in the decision between tolerance versus immune activation in response to dying cells. Thus, in the period of tumor cell death following chemotherapy or immunotherapy, the presence of IDO may help dictate the choice between dominant immunosuppression versus inflammation, antigen cross-presentation, and epitope spreading. The IDO pathway thus differs from other checkpoint-blockade strategies, in that it affects early immune responses, at the level of inflammation, activation of antigen-presenting cells, and initial cross-presentation of tumor antigens. This “up-stream” position may make IDO a potent target for therapeutic inhibition.",
keywords = "Checkpoint, Chemotherapy, IDO, Immunotherapy, Indoleamine 2,3-dioxygenase, Radiation, Tolerance, Tumor, Tumor microenvironment",
author = "Johnson, {Theodore Samuel} and McGaha, {Tracy L.} and Munn, {David H}",
year = "2017",
month = "1",
day = "1",
doi = "10.1007/978-3-319-67577-0_7",
language = "English (US)",
series = "Advances in Experimental Medicine and Biology",
publisher = "Springer New York LLC",
pages = "91--104",
booktitle = "Advances in Experimental Medicine and Biology",

}

TY - CHAP

T1 - Chemo-immunotherapy

T2 - Role of indoleamine 2,3-dioxygenase in defining immunogenic versus tolerogenic cell death in the tumor microenvironment

AU - Johnson, Theodore Samuel

AU - McGaha, Tracy L.

AU - Munn, David H

PY - 2017/1/1

Y1 - 2017/1/1

N2 - In certain settings, chemotherapy can trigger an immunogenic form of tumor cell death. More often, however, tumor cell death after chemotherapy is not immunogenic, and may be actively tolerizing. However, even in these settings the dying tumor cells may be much more immunogenic than previously recognized, if key suppressive immune checkpoints such as indoleamine 2,3-dioxygenase (IDO) can be blocked. This is an important question, because a robust immune response to dying tumor cells could potentially augment the efficacy of conventional chemotherapy, or enhance the strength and duration of response to other immunologic therapies. Recent findings using preclinical models of self-tolerance and autoimmunity suggest that IDO and related downstream pathways may play a fundamental role in the decision between tolerance versus immune activation in response to dying cells. Thus, in the period of tumor cell death following chemotherapy or immunotherapy, the presence of IDO may help dictate the choice between dominant immunosuppression versus inflammation, antigen cross-presentation, and epitope spreading. The IDO pathway thus differs from other checkpoint-blockade strategies, in that it affects early immune responses, at the level of inflammation, activation of antigen-presenting cells, and initial cross-presentation of tumor antigens. This “up-stream” position may make IDO a potent target for therapeutic inhibition.

AB - In certain settings, chemotherapy can trigger an immunogenic form of tumor cell death. More often, however, tumor cell death after chemotherapy is not immunogenic, and may be actively tolerizing. However, even in these settings the dying tumor cells may be much more immunogenic than previously recognized, if key suppressive immune checkpoints such as indoleamine 2,3-dioxygenase (IDO) can be blocked. This is an important question, because a robust immune response to dying tumor cells could potentially augment the efficacy of conventional chemotherapy, or enhance the strength and duration of response to other immunologic therapies. Recent findings using preclinical models of self-tolerance and autoimmunity suggest that IDO and related downstream pathways may play a fundamental role in the decision between tolerance versus immune activation in response to dying cells. Thus, in the period of tumor cell death following chemotherapy or immunotherapy, the presence of IDO may help dictate the choice between dominant immunosuppression versus inflammation, antigen cross-presentation, and epitope spreading. The IDO pathway thus differs from other checkpoint-blockade strategies, in that it affects early immune responses, at the level of inflammation, activation of antigen-presenting cells, and initial cross-presentation of tumor antigens. This “up-stream” position may make IDO a potent target for therapeutic inhibition.

KW - Checkpoint

KW - Chemotherapy

KW - IDO

KW - Immunotherapy

KW - Indoleamine 2,3-dioxygenase

KW - Radiation

KW - Tolerance

KW - Tumor

KW - Tumor microenvironment

UR - http://www.scopus.com/inward/record.url?scp=85039423936&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85039423936&partnerID=8YFLogxK

U2 - 10.1007/978-3-319-67577-0_7

DO - 10.1007/978-3-319-67577-0_7

M3 - Chapter

C2 - 29275467

AN - SCOPUS:85039423936

T3 - Advances in Experimental Medicine and Biology

SP - 91

EP - 104

BT - Advances in Experimental Medicine and Biology

PB - Springer New York LLC

ER -