Non-apoptotic Cell Death in Tumor Immunotherapy: Friend or Foe?

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Background

Immunotherapy is one of the most promising strategies to conquer cancer in the future. Immune checkpoint Inhibitors (ICIs) play a leading role in immunotherapy. However, only a small number of cancer patients benefit from immunotherapy. Therefore, developing novel immunotherapy strategies is mandatory. Targeting apoptosis-regulating molecules is ineffective in antitumor therapy since tumor cells resist apoptosis by evading recognition and killing by the immune system. Excitingly, non-apoptotic cell death exhibits distinguished functions in cancer immunotherapy. Non-apoptotic cell death includes ferroptosis, necroptosis, autophagy, and pyroptosis, and these processes can efficiently influence immune cell infiltration into the tumor microenvironment (TME) and response to immunotherapy. However, non-apoptotic cell death in tumor cells can also be a double-edged sword for tumor immunotherapy, for example, by inducing severe cytokine release syndrome. Thus, a deeper understanding of the role of non-apoptotic cell death in cancer is critical.

This research topic explores the current status of the role and mechanism of non-apoptotic cell death in tumor immunity. Firstly, we intend to provide an overview of how autophagy, pyroptosis, ferroptosis, and necroptosis influence the TME and the underlying mechanism. We will also explore how non-apoptotic cell death interacts with the TME elements, including immune cells and stromal cells. Secondly, as non-apoptotic cell death plays dual roles, including antagonism and synergy in antitumor immunity, potential pathways to circumvent this antagonism will be discussed. Thirdly, normal cells will also die when stimulated by damage-associated molecular patterns (DAMPs) released from the tumor cells through non- apoptotic cell death, hence, its mechanism and potential strategies to solve this problem will also be included in this topic. Finally, the combination of non-apoptotic cell death with other immunotherapy strategies (ICIs, CAR-T, et al.) and the effects of non-apoptotic cell death in different immunotherapy strategies will also be discussed.

We welcome submissions of relevant original research and reviews, including but not limited to the following topics:
• The role and mechanism of non-apoptotic cell death of tumor cells in tumor immunity;
• The detailed mechanisms of interaction between non-apoptotic cell death of tumor cells and TME;
• Discovery of novel non-apoptotic cell death processes or pathways in antitumor immunity.
• Novel drugs targeting non-apoptotic cell death and their functional mechanism in cancer immunotherapy;
• Strategies and mechanisms of evading the side effects of non-apoptotic cell death in antitumor immunity.


Please note: studies consisting solely of bioinformatic investigation of publicly available genomic/transcriptomic/proteomic data do not fall within the scope of the section unless they are expanded and provide significant biological or mechanistic insight into the process being studied and will not be accepted as part of this Research Topic.

Keywords: Non-apoptotic cell death, antitumor immunity, tumor microenvironment, immunotherapy, cancer

Important note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.

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