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Targeting Melanoma-Associated Fibroblasts (MAFs) with Activated γδ (Vδ2) T Cells: An In Vitro Cytotoxicity Model.

Anna Hajdara1,2, Uğur Çakır1, Barbara Érsek3

  • 1Department of Dermatology, Venereology and Dermatooncology, Semmelweis University, 1085 Budapest, Hungary.

International Journal of Molecular Sciences
|August 26, 2023
PubMed
Summary

Activated γδ T cells can kill melanoma-associated fibroblasts (MAFs) with zoledronic acid, enhancing anti-cancer therapy potential. This study investigated γδ T cell and MAF interactions in melanoma.

Keywords:
butyrophilincancercancer-associated fibroblastsmelanomamelanoma-associated fibroblaststumor microenvironmentzoledronic acidγδ T cells

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Area of Science:

  • Immunology
  • Oncology
  • Cell Biology

Background:

  • The tumor microenvironment (TME) influences cancer progression and immune evasion.
  • Cancer-associated fibroblasts (CAFs), or MAFs in melanoma, are key TME components.
  • γδ T cells are lymphocytes with potential in cancer immunotherapy, but responses vary.

Purpose of the Study:

  • To investigate the cytotoxic potential of activated γδ T cells against melanoma-derived MAFs.
  • To explore the mechanisms and factors influencing γδ T cell-mediated MAF killing.

Main Methods:

  • An in vitro platform was established using primary Vδ2 γδ T cells and patient-derived MAFs.
  • Zoledronic acid, anti-BTN3A1, anti-TCR γδ, and anti-BTN2A1 antibodies were used to modulate γδ T cell activity.
  • Apoptosis induction in MAFs was assessed.

Main Results:

  • Zoledronic acid (1-2.5 µM) was essential for inducing MAF apoptosis by γδ T cells.
  • An anti-BTN3A1 antibody (clone 20.1) enhanced γδ T cell cytotoxicity against MAFs.
  • Anti-TCR γδ and anti-BTN2A1 antibodies reduced this cytotoxic effect.

Conclusions:

  • Activated γδ T cells can eliminate MAFs, suggesting a novel therapeutic avenue for melanoma.
  • Zoledronic acid and specific antibody targeting (anti-BTN3A1) can enhance this anti-MAFF effect.
  • Findings support further clinical investigation of γδ T cell-based melanoma therapies.