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Fueling the Fire: Inflammatory Forms of Cell Death and Implications for Cancer Immunotherapy

Sheera R. Rosenbaum, Nicole A. Wilski and Andrew E. Aplin
Sheera R. Rosenbaum
1Department of Cancer Biology, Thomas Jefferson University, Philadelphia, Pennsylvania.
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Nicole A. Wilski
1Department of Cancer Biology, Thomas Jefferson University, Philadelphia, Pennsylvania.
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  • ORCID record for Nicole A. Wilski
Andrew E. Aplin
1Department of Cancer Biology, Thomas Jefferson University, Philadelphia, Pennsylvania.
2Sidney Kimmel Cancer Center, Philadelphia, Pennsylvania.
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  • For correspondence: Andrew.aplin@jefferson.edu
DOI: 10.1158/2159-8290.CD-20-0805 Published February 2021
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Abstract

Unleashing the immune system with immune checkpoint inhibitors (ICI) has significantly improved overall survival for subsets of patients with stage III/IV cancer. However, many tumors are nonresponsive to ICIs, in part due to a lack of tumor-infiltrating lymphocytes (TIL). Converting these immune “cold” tumors to “hot” tumors that are thus more likely to respond to ICIs is a major obstacle for cancer treatment. Triggering inflammatory forms of cell death, such as necroptosis and pyroptosis, may alter the tumor immune microenvironment and the influx of TILs. We present an emerging view that promoting tumor-localized necroptosis and pyroptosis may ultimately enhance responses to ICI.

Significance: Many tumor types respond poorly to ICIs or respond but subsequently acquire resistance. Effective therapies for ICI-nonresponsive tumors are lacking and should be guided by evidence from preclinical studies. Promoting inflammatory cell death mechanisms within the tumor may alter the local immune microenvironment toward an ICI-responsive state.

Footnotes

  • Cancer Discov 2021;11:266–81

  • Received June 8, 2020.
  • Revision received September 4, 2020.
  • Accepted October 1, 2020.
  • Published first January 15, 2021.
  • ©2021 American Association for Cancer Research.
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Cancer Discovery: 11 (2)
February 2021
Volume 11, Issue 2
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Fueling the Fire: Inflammatory Forms of Cell Death and Implications for Cancer Immunotherapy
Sheera R. Rosenbaum, Nicole A. Wilski and Andrew E. Aplin
Cancer Discov February 1 2021 (11) (2) 266-281; DOI: 10.1158/2159-8290.CD-20-0805

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Fueling the Fire: Inflammatory Forms of Cell Death and Implications for Cancer Immunotherapy
Sheera R. Rosenbaum, Nicole A. Wilski and Andrew E. Aplin
Cancer Discov February 1 2021 (11) (2) 266-281; DOI: 10.1158/2159-8290.CD-20-0805
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    • Abstract
    • Introduction
    • Inflammatory Cell Death
    • Immune Response to Inflammatory Cell Death
    • Inflammatory Cell Death in Cancer
    • The Potential for Synergy Between Immune Checkpoint Blockade and Inflammatory Cell Death–inducing Therapies
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  • Modes of Regulated Cell Death in Cancer
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