Targeting novel regulated cell death: Ferroptosis, pyroptosis and necroptosis in anti‐PD‐1/PD‐L1 cancer immunotherapy

Author:

Yu Li12ORCID,Huang Ke1,Liao Yixiang2,Wang Lingzhi345,Sethi Gautam35ORCID,Ma Zhaowu1ORCID

Affiliation:

1. Health Science Center Yangtze University Jingzhou Hubei China

2. Department of Urology Jingzhou Central Hospital, Jingzhou Hospital Affiliated to Yangtze University Jingzhou Hubei China

3. Department of Pharmacology Yong Loo Lin School of Medicine, National University of Singapore Singapore Singapore

4. Cancer Science Institute of Singapore, National University of Singapore Singapore Singapore

5. NUS Centre for Cancer Research (N2CR), National University of Singapore Singapore Singapore

Abstract

AbstractChemotherapy, radiotherapy, and immunotherapy represent key tumour treatment strategies. Notably, immune checkpoint inhibitors (ICIs), particularly anti‐programmed cell death 1 (PD1) and anti‐programmed cell death ligand 1 (PD‐L1), have shown clinical efficacy in clinical tumour immunotherapy. However, the limited effectiveness of ICIs is evident due to many cancers exhibiting poor responses to this treatment. An emerging avenue involves triggering non‐apoptotic regulated cell death (RCD), a significant mechanism driving cancer cell death in diverse cancer treatments. Recent research demonstrates that combining RCD inducers with ICIs significantly enhances their antitumor efficacy across various cancer types. The use of anti‐PD‐1/PD‐L1 immunotherapy activates CD8+ T cells, prompting the initiation of novel RCD forms, such as ferroptosis, pyroptosis, and necroptosis. However, the functions and mechanisms of non‐apoptotic RCD in anti‐PD1/PD‐L1 therapy remain insufficiently explored. This review summarises the emerging roles of ferroptosis, pyroptosis, and necroptosis in anti‐PD1/PD‐L1 immunotherapy. It emphasises the synergy between nanomaterials and PD‐1/PD‐L1 inhibitors to induce non‐apoptotic RCD in different cancer types. Furthermore, targeting cell death signalling pathways in combination with anti‐PD1/PD‐L1 therapies holds promise as a prospective immunotherapy strategy for tumour treatment.

Publisher

Wiley

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