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Immune checkpoint inhibitors in melanoma: mechanisms, immune cell interactions, and the tumour microenvironment

Yiwen Liang1, Yan Zheng1, Yuyan Zeng2

  • 1Medical School, Hunan University of Chinese Medicine, Changsha, Hunan, China.

Frontiers in Immunology
|December 5, 2025
PubMed

Insights

Immune checkpoint inhibitors (ICIs) show promise for melanoma, but not all patients respond. Understanding immune cell and tumor microenvironment interactions is key to improving ICI therapy for melanoma.

Area of Science:

  • Oncology
  • Immunology
  • Dermatology

Background:

  • Melanoma is an aggressive skin cancer with rising incidence and limited traditional therapy options.
  • Immune checkpoint inhibitors (ICIs) have revolutionized melanoma treatment by harnessing the immune system.
  • Treatment resistance and non-response to ICIs highlight the need for deeper understanding of complex tumor-immune interactions.

Purpose of the Study:

  • To comprehensively review the mechanisms of ICIs in melanoma.
  • To explore the roles of diverse immune cells and the tumor microenvironment (TME) in ICI efficacy.
  • To elucidate the impact of disease stage and skin-specific factors on immunotherapy outcomes.

Main Methods:

  • Literature review of immune checkpoint inhibitors in melanoma.
  • Analysis of immune cell functions (T cells, NK cells, macrophages, etc.) in the TME.
  • Examination of the TME's influence on therapeutic responses.

Main Results:

  • ICIs activate antitumor immunity but face challenges like resistance and non-response.
  • Various immune cells and TME components significantly modulate ICI efficacy.
  • Skin-specific immune cells and the skin microbiome play crucial roles in melanoma immunotherapy.

Conclusions:

  • Optimizing ICI therapy requires a thorough understanding of immune cell and TME dynamics in melanoma.
  • Tailoring immunotherapy strategies based on disease stage and microenvironmental factors is essential.
  • Further research into these interactions can provide new theoretical foundations for advanced melanoma treatment.
Keywords:
adjuvant therapyimmune cellsimmune checkpoint inhibitorsmelanomaneoadjuvant therapytissue-resident memory T cellstumor microenvironmenttumor staging

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