Biomedicine & Pharmacotherapy (Jun 2024)

Targeting BTLA with the peptide inhibitor HVEM(14-39) – A new way to restore the activity of T cells in melanoma

  • Karolina Wojciechowicz,
  • Katarzyna Kuncewicz,
  • Jacek Rutkowski,
  • Jacek Jassem,
  • Sylwia Rodziewicz-Motowidło,
  • Anna Wardowska,
  • Marta Spodzieja

Journal volume & issue
Vol. 175
p. 116675

Abstract

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The complex of B- and T-lymphocyte attenuator (BTLA) and herpes virus entry mediator (HVEM) plays a critical role in immune regulation and has emerged as a promising therapeutic target for cancer treatment. In this study, we investigated the potential of the peptide inhibitor HVEM(14-39) to restore peripheral T cell activity in patients with advanced melanoma. In these patients, CD8+ T cells downregulated BTLA expression and increased HVEM expression upon activation. The addition of HVEM(14-39) reduced the percentage of BTLA+ CD8+ T cells and increased the subpopulation of HVEM+ CD8+ T cells. Additionally, HVEM(14-39) enhanced T cell activation, proliferation, and the shift toward effector memory T cell subpopulations. Finally, this peptide affected the proliferation rate and late apoptosis of melanoma cell line in co-culture with T cells. These findings suggest that HVEM(14-39) can overcome T cell exhaustion and improve antitumor responses. Peptide-based immunotherapy targeting the BTLA-HVEM complex offers a promising alternative to monoclonal antibody-based therapies, with the potential for fewer side effects and higher treatment efficacy.

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