Research
Print page Print page
Switch language
The Capital Region of Denmark - a part of Copenhagen University Hospital
Published

The metabolic enzyme arginase-2 is a potential target for novel immune modulatory vaccines

Research output: Contribution to journalJournal articleResearchpeer-review

  1. Staphylococcus aureus alpha-toxin inhibits CD8+ T cell-mediated killing of cancer cells in cutaneous T-cell lymphoma

    Research output: Contribution to journalJournal articleResearchpeer-review

  2. Neo-antigen specific memory T-cell responses in healthy individuals

    Research output: Contribution to journalJournal articleResearchpeer-review

  3. Immunoprofiles of colorectal cancer from Lynch syndrome

    Research output: Contribution to journalJournal articleResearchpeer-review

  4. Staphylococcal alpha-toxin tilts the balance between malignant and non-malignant CD4+ T cells in cutaneous T-cell lymphoma

    Research output: Contribution to journalJournal articleResearchpeer-review

  5. T cell recognition of novel shared breast cancer antigens is frequently observed in peripheral blood of breast cancer patients

    Research output: Contribution to journalJournal articleResearchpeer-review

  1. Cytotoxic T cells isolated from healthy donors and cancer patients kill TGFβ-expressing cancer cells in a TGFβ-dependent manner

    Research output: Contribution to journalJournal articleResearchpeer-review

  2. The Thioredoxin-Interacting Protein TXNIP Is a Putative Tumour Suppressor in Cutaneous T-Cell Lymphoma

    Research output: Contribution to journalJournal articleResearchpeer-review

  3. Changes in the Tumor Immune Microenvironment during Disease Progression in Patients with Ovarian Cancer

    Research output: Contribution to journalJournal articleResearchpeer-review

  4. The risk of cardiac events in patients receiving immune checkpoint inhibitors: a nationwide Danish study

    Research output: Contribution to journalJournal articleResearchpeer-review

View graph of relations

One way that tumors evade immune destruction is through tumor and stromal cell expression of arginine-degrading enzyme arginase-2 (ARG2). Here we describe the existence of pro-inflammatory effector T-cells that recognize ARG2 and can directly target tumor and tumor-infiltrating cells. Using a library of 34 peptides covering the entire ARG2 sequence, we examined reactivity toward these peptides in peripheral blood mononuclear cells from cancer patients and healthy individuals. Interferon-γ ELISPOT revealed frequent immune responses against several of the peptides, indicating that ARG2-specific self-reactive T-cells are natural components of the human T-cell repertoire. Based on this, the most immunogenic ARG2 protein region was further characterized. By identifying conditions in the microenvironment that induce ARG2 expression in myeloid cells, we showed that ARG2-specific CD4T-cells isolated and expanded from a peripheral pool from a prostate cancer patient could recognize target cells in an ARG2-dependent manner. In the 'cold' in vivo tumor model Lewis lung carcinoma, we found that activation of ARG2-specific T-cells by vaccination significantly inhibited tumor growth. Immune-modulatory vaccines targeting ARG2 thus are a candidate strategy for cancer immunotherapy.

Original languageEnglish
JournalOncoImmunology
Volume9
Issue number1
Pages (from-to)1771142
ISSN2162-4011
DOIs
Publication statusPublished - 1 Jun 2020

ID: 61243545