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Ferroptosis, pyroptosis, and necroptosis in melanoma: regulatory cell death pathways and their implications for

Qingyi Wang1, Jian Zhu2

  • 1Department of Dermatology, Qingdao Hospital of University of Health and Rehabilitation Sciences Qingdao Municipal Hospital (Group), Qingdao, Shandong, China.

Frontiers in Oncology
|May 25, 2026
PubMed

Insights

Regulated cell death pathways like ferroptosis, pyroptosis, and necroptosis show promise for overcoming challenges in melanoma immunotherapy by enhancing anti-tumor immunity and improving patient outcomes.

Area of Science:

  • Oncology
  • Immunology
  • Cell Biology

Background:

  • Melanoma is an aggressive skin cancer with poor outcomes in advanced stages.
  • Immune checkpoint inhibitors (ICIs) have improved melanoma treatment but face challenges like resistance and toxicity.
  • Novel regulated cell death (RCD) pathways offer potential solutions.

Purpose of the Study:

  • To review the mechanisms of ferroptosis, pyroptosis, and necroptosis in melanoma.
  • To explore their role in modulating the tumor immune microenvironment (TME) and immunogenicity.
  • To discuss their combination with ICIs for enhanced immunotherapy.

Main Methods:

  • Systematic review of molecular mechanisms.
  • Analysis of RCD pathways' influence on melanoma progression and immunotherapy response.
  • Exploration of synergistic interactions between RCD and ICIs.

Main Results:

  • Ferroptosis, pyroptosis, and necroptosis can remodel the TME and boost anti-tumor immunity.
  • These RCD pathways hold potential to overcome ICI resistance and toxicity.
  • Synergistic effects between RCD induction and ICIs can potentiate anti-tumor responses.

Conclusions:

  • Targeting ferroptosis, pyroptosis, and necroptosis presents a promising strategy for melanoma immunotherapy.
  • Therapeutic strategies inducing these RCD modalities can improve clinical outcomes.
  • Further research into RCD pathways offers new avenues for melanoma treatment.
Keywords:
ferroptosisimmunotherapymelanomanecroptosispyroptosis

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