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Pyroptosis and the fight against lung cancer
Jiwei Wang1,2,3, Huiling Su2,3, Min Wang2,3
1State Key Laboratory of Primate Biomedical Research, Kunming University of Science and Technology, Kunming, China.
Abstract:
Pyroptosis, a newly characterized type of inflammatory programmed cell death (PCD), is usually triggered by multiple inflammasomes which can recognize different danger or damage-associated molecular patterns (DAMPs), leading to the activation of caspase-1 and the cleavage of gasdermin D (GSDMD). Gasdermin family pore-forming proteins are the executers of pyroptosis and are normally maintained in an inactive state through auto-inhibition. Upon caspases mediated cleavage of gasdermins, the pro-pyroptotic N-terminal fragment is released from the auto-inhibition of C-terminal fragment and oligomerizes, forming pores in the plasma membrane. This results in the secretion of interleukin (IL)-1β, IL-18, and high-mobility group box 1 (HMGB1), generating osmotic swelling and lysis. Current therapeutic approaches including chemotherapy, radiotherapy, molecularly targeted therapy and immunotherapy for lung cancer treatment efficiently force the cancer cells to undergo pyroptosis, which then generates local and systemic antitumor immunity. Thus, pyroptosis is recognized as a new therapeutic regimen for the treatment of lung cancer. In this review, we briefly describe the signaling pathways involved in pyroptosis, and endeavor to discuss the antitumor effects of pyroptosis and its potential application in lung cancer therapy, focusing on the contribution of pyroptosis to microenvironmental reprogramming and evocation of antitumor immune response.
Insights
Pyroptosis, an inflammatory cell death, involves inflammasomes and gasdermin D cleavage, leading to cell lysis and cytokine release. This process shows promise as a new lung cancer therapy by stimulating antitumor immunity.
Area of Science:
- Immunology
- Cell Biology
- Oncology
Background:
- Pyroptosis is an inflammatory programmed cell death (PCD) pathway.
- It is triggered by inflammasomes recognizing danger signals, activating caspase-1 and cleaving gasdermin D (GSDMD).
- Gasdermin D cleavage releases N-terminal fragments that form pores in the cell membrane, causing cell lysis and release of inflammatory cytokines like IL-1β and IL-18.
Purpose of the Study:
- To review the signaling pathways of pyroptosis.
- To discuss the antitumor effects of pyroptosis in lung cancer.
- To explore pyroptosis's potential as a therapeutic strategy for lung cancer by reprogramming the tumor microenvironment and evoking immune responses.
Main Methods:
- Literature review of pyroptosis mechanisms and signaling pathways.
- Analysis of current lung cancer therapeutic approaches that induce pyroptosis.
- Discussion of pyroptosis's role in modulating the tumor microenvironment and immune response.
Main Results:
- Pyroptosis execution involves caspase-mediated cleavage of gasdermins, leading to plasma membrane pore formation.
- Induction of pyroptosis in lung cancer cells via chemotherapy, radiotherapy, targeted therapy, or immunotherapy generates local and systemic antitumor immunity.
- Pyroptosis contributes to microenvironmental reprogramming and the evocation of antitumor immune responses.
Conclusions:
- Pyroptosis is a key inflammatory cell death pathway with significant implications for cancer therapy.
- Pyroptosis-inducing strategies represent a promising new therapeutic regimen for lung cancer.
- Further research into pyroptosis mechanisms can optimize its application in lung cancer treatment.
