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Analysis of Human T Cell Activity in an Allogeneic Co-Culture Setting of Pre-Treated Tumor Cells
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Mechanism and role of regulated cell death in tumor immunity and immunotherapy

Jingwen Hu1,2, Yan Li1,2, Bingjie Lian1,2

  • 1Department of Pathology, Xiangya Hospital, Central South University, Changsha, Hunan, P. R. China.

Cancer Communications (London, England)
|September 26, 2025
PubMed

Insights

Targeting non-apoptotic regulated cell death (RCD) pathways like ferroptosis and pyroptosis can enhance cancer immunotherapy. Inducing these cell death types may overcome resistance and transform tumors, improving patient outcomes.

Area of Science:

  • Oncology
  • Immunotherapy
  • Cell Death Research

Background:

  • Immune checkpoint inhibitors (ICIs) show limited efficacy in about two-thirds of cancer patients.
  • Non-apoptotic regulated cell death (RCD) pathways are emerging as novel cancer therapy targets.
  • RCDs release damage-associated molecular patterns (DAMPs), crucial for immune response activation.

Purpose of the Study:

  • To systematically review the mechanisms and immunomodulatory functions of five non-apoptotic RCD subtypes.
  • To discuss current treatment strategies involving ferroptosis, necroptosis, autophagy, cuproptosis, and pyroptosis.
  • To explore the potential of RCD induction in combination with existing immunotherapies.

Main Methods:

  • Systematic literature review of non-apoptotic regulated cell death (RCD) mechanisms.
  • Analysis of RCD subtypes: ferroptosis, necroptosis, autophagy, cuproptosis, and pyroptosis.
  • Evaluation of RCD-inducing agents (small molecules, nanoparticles) and their therapeutic effects.

Main Results:

  • Non-apoptotic RCDs can release DAMPs, enhance antigen presentation, and remodel the tumor immune microenvironment.
  • Targeting RCD pathways can reverse resistance to chemoradiotherapy and ICIs, converting 'cold' to 'hot' tumors.
  • Induction of RCD promotes anti-tumor immune responses and establishes durable immune memory.

Conclusions:

  • Non-apoptotic RCD pathways offer a promising strategy to enhance cancer immunotherapy efficacy.
  • Precise induction of RCD can overcome treatment resistance and improve anti-tumor immunity.
  • Combination therapies involving RCD induction and ICIs hold significant potential for future cancer treatment.
Keywords:
regulated cell deathtumor immune microenvironmenttumor immunitytumor immunotherapy

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