BROWSE

Related Researcher

Author's Photo

Lee, SangJoon
Research Interests

ITEM VIEW & DOWNLOAD

Inflammatory Cell Death, PANoptosis, Mediated by Cytokines in Diverse Cancer Lineages Inhibits Tumor Growth

Cited 0 times inthomson ciCited 0 times inthomson ci
Title
Inflammatory Cell Death, PANoptosis, Mediated by Cytokines in Diverse Cancer Lineages Inhibits Tumor Growth
Author
Malireddi, R. K. SubbaraoKarki, RajendraSundaram, BalamuruganKancharana, BalabhaskararaoLee, SangJoonSamir, ParimalKanneganti, Thirumala-Devi
Issue Date
2021-03
Publisher
American Association of Immunologists, Inc.
Citation
ImmunoHorizons, v.5, no.7, pp.568 - 580
Abstract
Resistance to cell death is a hallmark of cancer. Immunotherapy, particularly immune checkpoint blockade therapy, drives immune-mediated cell death and has greatly improved treatment outcomes for some patients with cancer, but it often fails clinically. Its success relies on the cytokines and cytotoxic functions of effector immune cells to bypass the resistance to cell death and eliminate cancer cells. However, the specific cytokines capable of inducing cell death in tumors and the mechanisms that connect cytokines to cell death across cancer cell types remain unknown. In this study, we analyzed expression of several cytokines that are modulated in tumors and found correlations between cytokine expression and mortality. Of several cytokines tested for their ability to kill cancer cells, only TNF-α and IFN-γ together were able to induce cell death in 13 distinct human cancer cell lines derived from colon and lung cancer, melanoma, and leukemia. Further evaluation of the specific programmed cell death pathways activated by TNF-α and IFN-γ in these cancer lines identified PANoptosis, a form of inflammatory cell death that was previously shown to be activated by contemporaneous engagement of components from pyroptosis, apoptosis, and/or necroptosis. Specifically, TNF-α and IFN-γ triggered activation of gasdermin D, gasdermin E, caspase-8, caspase-3, caspase-7, and MLKL. Furthermore, the intratumoral administration of TNF-α and IFN-γ suppressed the growth of transplanted xenograft tumors in an NSG mouse model. Overall, this study shows that PANoptosis, induced by synergism of TNF-α and IFN-γ, is an important mechanism to kill cancer cells and suppress tumor growth that could be therapeutically targeted.
URI
https://scholarworks.unist.ac.kr/handle/201301/57778
DOI
10.4049/immunohorizons.2100059
ISSN
2573-7732
Appears in Collections:
BIO_Journal Papers
Files in This Item:
568.full.pdf Download

find_unist can give you direct access to the published full text of this article. (UNISTARs only)

Show full item record

qrcode

  • mendeley

    citeulike

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.

MENU