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Theranostics 2021; 11(18):8813-8835. doi:10.7150/thno.62521 This issue Cite

Review

Inflammation-related pyroptosis, a novel programmed cell death pathway, and its crosstalk with immune therapy in cancer treatment

Sheng-Kai Hsu¹, Chia-Yang Li², I-Ling Lin³, Wun-Jyun Syue¹, Yih-Fung Chen⁴, Kai-Chun Cheng^5,6, Yen-Ni Teng⁷, Yi-Hsiung Lin^8,9,10, Chia-Hung Yen⁴, Chien-Chih Chiu^{1,2,11,12,13✉}

1. Department of Biotechnology, Kaohsiung Medical University, Kaohsiung 807, Taiwan.
2. Graduate Institute of Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan.
3. Department of Medical Laboratory Science and Biotechnology, Kaohsiung Medical University, Kaohsiung 807, Taiwan.
4. Graduate Institute of Natural Products, Kaohsiung Medical University, Kaohsiung 807, Taiwan.
5. Department of Ophthalmology, Kaohsiung Municipal Hsiaokang Hospital, Kaohsiung 812, Taiwan.
6. Department of Ophthalmology, Kaohsiung Medical University Hospital, Kaohsiung 807, Taiwan.
7. Department of Biological Sciences and Technology, National University of Tainan, Tainan 700, Taiwan.
8. Division of Cardiology, Department of Internal Medicine, Kaohsiung Medical University Hospital.
9. Center for Lipid Biosciences, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.
10. Lipid Science and Aging Research Center, Kaohsiung Medical University, Kaohsiung, Taiwan.
11. Department of Biological Sciences, National Sun Yat-sen University, Kaohsiung 804, Taiwan.
12. Center for Cancer Research, Kaohsiung Medical University, Kaohsiung, 807, Taiwan.
13. Department of Medical Research, Kaohsiung Medical University Hospital, Kaohsiung 807, Taiwan.

✉ Corresponding author: E-mail: cchiuedu.tw (C.-C.C.); Tel.: +886-7-3121101 (ext. 2368); Fax: +886-7-312-5339.

Abstract

In recent decades, chemotherapies targeting apoptosis have emerged and demonstrated remarkable achievements. However, emerging evidence has shown that chemoresistance is mediated by impairing or bypassing apoptotic cell death. Several novel types of programmed cell death, such as ferroptosis, necroptosis, and pyroptosis, have recently been reported to play significant roles in the modulation of cancer progression and are considered a promising strategy for cancer treatment. Thus, the switch between apoptosis and pyroptosis is also discussed. Cancer immunotherapy has gained increasing attention due to breakthroughs in immune checkpoint inhibitors; moreover, ferroptosis, necroptosis, and pyroptosis are highly correlated with the modulation of immunity in the tumor microenvironment. Compared with necroptosis and ferroptosis, pyroptosis is the primary mechanism for host defense and is crucial for bridging innate and adaptive immunity. Furthermore, recent evidence has demonstrated that pyroptosis exerts benefits on cancer immunotherapies, including immune checkpoint inhibitors (ICIs) and chimeric antigen receptor T-cell therapy (CAR-T). Hence, in this review, we elucidate the role of pyroptosis in cancer progression and the modulation of immunity. We also summarize the potential small molecules and nanomaterials that target pyroptotic cell death mechanisms and their therapeutic effects on cancer.

Keywords: Nonapoptotic programmed cell death, pyroptosis, inflammasome, cell death switch, immunotherapy

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