Arginase-1-based vaccination against the tumor microenvironment: the identification of an optimal T-cell epitope

10 Citations (Scopus)


L-arginine depletion by regulatory cells and cancer cells expressing arginase-1 (Arg-1) is a vital contributor to the immunosuppressive tumor microenvironment in patients with cancer. We have recently described the existence of pro-inflammatory effector T cells that recognize Arg-1. Hence, Arg-1-specific self-reactive T cells are a naturally occurring part of the memory T-cell repertoire of the human immune system. Here, we further characterize a highly immunogenic epitope from Arg-1. We describe frequent T-cell-based immune responses against this epitope in patients with cancer, as well as in healthy donors. Furthermore, we show that Arg-1-specific T cells expand in response to the TH2 cytokine interleukin (IL)-4 without any specific stimulation. Arg-1-specific memory TH1 cells that respond to increased IL-4 concentration may, therefore, drive the immune response back into the TH1 pathway. Arg-1-specific T cells thus appear to have an important function in immune regulation. Because Arg-1 plays an important role in the immunosuppressive microenvironment in most cancers, an immune modulatory vaccination approach can readily be employed to tilt the balance away from immune suppression in these settings.

Original languageEnglish
JournalCancer immunology, immunotherapy
Issue number11
Pages (from-to)1901-1907
Number of pages7
Publication statusPublished - Nov 2019


  • Animals
  • Arginase/immunology
  • Cancer Vaccines/administration & dosage
  • Epitopes, T-Lymphocyte/immunology
  • Humans
  • Neoplasms/immunology
  • T-Lymphocytes/immunology
  • Tumor Microenvironment/immunology
  • Vaccination
  • IO112
  • Arginase
  • PIVAC 18
  • Anti-regulatory T cells
  • Immune-modulating vaccines


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