Induced Necroptosis and Its Role in Cancer Immunotherapy

Int J Mol Sci. 2024 Oct 6;25(19):10760. doi: 10.3390/ijms251910760.

Abstract

Necroptosis is a type of regulated cell death (RCD) that is triggered by changes in the extracellular or intracellular milieu that are picked up by certain death receptors. Thanks to its potent capacity to induce immunological responses and overcome apoptotic resistance, it has garnered significant attention as a potential cancer treatment. Basic information for the creation of nano-biomedical treatments is provided by studies on the mechanisms underlying tumor necroptosis. Receptor-interacting protein kinase 1 (RIPK1)-RIPK3-mediated necroptosis, Toll-like receptor domain-containing adapter-inducing interferon (IFN)-β (TRIF)-RIPK3-mediated necroptosis, Z-DNA-binding protein 1 (ZBP1)-RIPK3-mediated necroptosis, and IFNR-mediated necroptosis are the four signaling pathways that collectively account for triggered necroptosis in this review. Necroptosis has garnered significant interest as a possible cancer treatment strategy because, in contrast to apoptosis, it elicits immunological responses that are relevant to therapy. Thus, a thorough discussion is held on the connections between tumor cell necroptosis and the immune environment, cancer immunosurveillance, and cells such as dendritic cells (DCs), cytotoxic T cells, natural killer (NK) cells, natural killer T (NKT) cells, and their respective cytokines. Lastly, a summary of the most recent nanomedicines that cause necroptosis in order to cause immunogenic cell death is provided in order to emphasize their promise for cancer immunotherapy.

Keywords: DAMPs; cancer immunotherapy; immune microenvironment; immunogenic cell death; necroptosis.

Publication types

  • Review

MeSH terms

  • Animals
  • Humans
  • Immunotherapy* / methods
  • Necroptosis* / immunology
  • Neoplasms* / immunology
  • Neoplasms* / pathology
  • Neoplasms* / therapy
  • Receptor-Interacting Protein Serine-Threonine Kinases / metabolism
  • Signal Transduction

Substances

  • Receptor-Interacting Protein Serine-Threonine Kinases

Grants and funding

The authors’ research is supported by the Postdoctoral Fellowship Program of CPSF (GZC20230196) and the National Natural Science Foundation of China (52273118 and 22275013). Many thanks for the funding support of the Open Project of Key Laboratory of Advanced Materials of the Ministry of Education, Tsinghua University (AdvMat-2023-8) and the union project of BUCT-CJFH biomedical center (PT2407, 2024-NHLHCRF-YXHZ-MS-05).