Therapy-Induced Tumor Cell Death: Friend or Foe of Immunotherapy?

Combinatory treatments using surgery, radiotherapy and/or chemotherapy together with immunotherapy have shown encouraging results for specific subsets of tumors, but a significant proportion of tumors remains unsusceptible. Some of these inconsistencies are thought to be the consequence of an immuno...

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Published inFrontiers in oncology Vol. 11; p. 678562
Main Authors van Schaik, Thijs A., Chen, Kok-Siong, Shah, Khalid
Format Journal Article
LanguageEnglish
Published Frontiers Media S.A 01.06.2021
Subjects
damage associated molecular pattern (DAMP)
immunogenic
immunotherapy
Oncology
tolerogenic
tumor cell death
tumor microenvironment (TME)
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Abstract Combinatory treatments using surgery, radiotherapy and/or chemotherapy together with immunotherapy have shown encouraging results for specific subsets of tumors, but a significant proportion of tumors remains unsusceptible. Some of these inconsistencies are thought to be the consequence of an immunosuppressive tumor microenvironment (TME) caused by therapy-induced tumor cell death (TCD). An increased understanding of the molecular mechanisms governing TCD has provided valuable insights in specific signaling cascades activated by treatment and the subsequent effects on the TME. Depending on the treatment variables of conventional chemo-, radio- and immunotherapy and the genetic composition of the tumor cells, particular cell death pathways are activated. Consequently, TCD can either have tolerogenic or immunogenic effects on the local environment and thereby affect the post-treatment anti-tumor response of immune cells. Thus, identification of these events can provide new rationales to increase the efficacy of conventional therapies combined with immunotherapies. In this review, we sought to provide an overview of the molecular mechanisms initiated by conventional therapies and the impact of treatment-induced TCD on the TME. We also provide some perspectives on how we can circumvent tolerogenic effects by adequate treatment selection and manipulation of key signaling cascades.
AbstractList Combinatory treatments using surgery, radiotherapy and/or chemotherapy together with immunotherapy have shown encouraging results for specific subsets of tumors, but a significant proportion of tumors remains unsusceptible. Some of these inconsistencies are thought to be the consequence of an immunosuppressive tumor microenvironment (TME) caused by therapy-induced tumor cell death (TCD). An increased understanding of the molecular mechanisms governing TCD has provided valuable insights in specific signaling cascades activated by treatment and the subsequent effects on the TME. Depending on the treatment variables of conventional chemo-, radio- and immunotherapy and the genetic composition of the tumor cells, particular cell death pathways are activated. Consequently, TCD can either have tolerogenic or immunogenic effects on the local environment and thereby affect the post-treatment anti-tumor response of immune cells. Thus, identification of these events can provide new rationales to increase the efficacy of conventional therapies combined with immunotherapies. In this review, we sought to provide an overview of the molecular mechanisms initiated by conventional therapies and the impact of treatment-induced TCD on the TME. We also provide some perspectives on how we can circumvent tolerogenic effects by adequate treatment selection and manipulation of key signaling cascades.
Author van Schaik, Thijs A.
Shah, Khalid
Chen, Kok-Siong
AuthorAffiliation 2 Department of Neurosurgery, Brigham and Women’s Hospital, Harvard Medical School , Boston, MA , United States
1 Center for Stem Cell Therapeutics and Imaging (CSTI), Harvard Medical School , Boston, MA , United States
3 Harvard Stem Cell Institute, Harvard University , Cambridge, MA , United States
AuthorAffiliation_xml – name: 3 Harvard Stem Cell Institute, Harvard University , Cambridge, MA , United States
– name: 1 Center for Stem Cell Therapeutics and Imaging (CSTI), Harvard Medical School , Boston, MA , United States
– name: 2 Department of Neurosurgery, Brigham and Women’s Hospital, Harvard Medical School , Boston, MA , United States
Author_xml – sequence: 1
  givenname: Thijs A.
  surname: van Schaik
  fullname: van Schaik, Thijs A.
– sequence: 2
  givenname: Kok-Siong
  surname: Chen
  fullname: Chen, Kok-Siong
– sequence: 3
  givenname: Khalid
  surname: Shah
  fullname: Shah, Khalid
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Edited by: Oliver Kepp, Institut National de la Santé et de la Recherche Médicale (INSERM), France
Reviewed by: Udo S. Gaipl, University Hospital Erlangen, Germany; Lucillia Bezu, Gustave Roussy Cancer Campus, France
This article was submitted to Molecular and Cellular Oncology, a section of the journal Frontiers in Oncology
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SecondaryResourceType review_article
Snippet Combinatory treatments using surgery, radiotherapy and/or chemotherapy together with immunotherapy have shown encouraging results for specific subsets of...
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pubmedcentral
proquest
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Open Access Repository
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StartPage 678562
SubjectTerms damage associated molecular pattern (DAMP)
immunogenic
immunotherapy
Oncology
tolerogenic
tumor cell death
tumor microenvironment (TME)
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Title Therapy-Induced Tumor Cell Death: Friend or Foe of Immunotherapy?
URI https://search.proquest.com/docview/2543445333
https://pubmed.ncbi.nlm.nih.gov/PMC8204251
https://doaj.org/article/2afd9c649b214a8c9f384dc7ef75cfdd
Volume 11
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