Arginase-1 specific CD8+ T cells react toward malignant and regulatory myeloid cells

Hannah Jorinde Glöckner, Evelina Martinenaite, Thomas Landkildehus Lisle, Jacob Grauslund, Shamaila Ahmad, Özcan Met, Per Thor Straten, Mads Hald Andersen*

*Corresponding author for this work

Research output: Contribution to journalJournal articleResearchpeer-review

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Abstract

Arginase-1 (Arg1) is expressed by regulatory myeloid cells in the tumor microenvironment (TME), where they play a pro-tumorigenic and T-cell suppressive role. Arg1-specific CD4+ and CD8+ memory T cells have been observed in both healthy individuals and cancer patients. However, while the function of anti-regulatory Arg1-specific CD4+ T cells has been characterized, our knowledge of CD8+ Arg1-specific T cells is only scarce. In the current study, we describe the immune-modulatory capabilities of CD8+ Arg1-specific T cells. We generated CD8+ Arg1-specific T cell clones to target Arg1-expressing myeloid cells. Our results demonstrate that these T cells recognize both malignant and nonmalignant regulatory myeloid cells in an Arg1-expression-dependent manner. Notably, Arg1-specific CD8+ T cells possess cytolytic effector capabilities. Immune modulatory vaccines (IMVs) represent a novel treatment modality for cancer. The activation of Arg1-specific CD8+ T cells through Arg1-based IMVs can contribute to the modulatory effects of this treatment strategy.

Original languageEnglish
Article number2318053
JournalOncoImmunology
Volume13
Issue number1
Number of pages9
ISSN2162-4011
DOIs
Publication statusPublished - 2024

Keywords

  • Anti-regulatory T cells
  • Arginase-1
  • Immune modulatory vaccines
  • Myeloid cells
  • Tumor microenvironment

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