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

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  1. Evidence of immune elimination, immuno-editing and immune escape in patients with hematological cancer

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  2. TAM-ing T cells in the tumor microenvironment: implications for TAM receptor targeting

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  3. Tumor-induced escape mechanisms and their association with resistance to checkpoint inhibitor therapy

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  4. Cancer immunotherapy in patients with brain metastases

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  5. NY-ESO-1- and survivin-specific T-cell responses in the peripheral blood from patients with glioma

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  1. Author Correction: Mutational and putative neoantigen load predict clinical benefit of adoptive T cell therapy in melanoma

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  2. Author Correction: Tertiary lymphoid structures improve immunotherapy and survival in melanoma

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  3. CTLA-4 blockade boosts the expansion of tumor-reactive CD8+ tumor-infiltrating lymphocytes in ovarian cancer

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  4. Evidence of immune elimination, immuno-editing and immune escape in patients with hematological cancer

    Research output: Contribution to journalReviewResearchpeer-review

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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 : CII
Volume68
Issue number11
Pages (from-to)1901-1907
Number of pages7
ISSN0340-7004
DOIs
Publication statusPublished - Nov 2019

    Research areas

  • 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

ID: 58520988