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

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.

KEYWORDS:

• Arginase-1
• anti-regulatory T cells
• immune modulatory vaccines
• myeloid cells
• tumor microenvironment

Acknowledgments

We would like to thank Merete Jonassen, Anette Højgaard Andersen and Tina Seremet for excellent technical assistance. This work was supported by Herlev and Gentofte Hospital, and through a research funding agreement between IO Biotech ApS and National Center for Cancer Immune Therapy (CCIT-DK).

Disclosure statement

Mads Hald Andersen is named as an inventor on various patent applications relating to therapeutic uses of arginase peptides. These patent applications are assigned to the company IO Biotech ApS, which is developing immune-modulating cancer treatments. Mads Hald Andersen is founder, shareholder and advisor of IO Biotech ApS. Evelina Martinenaite is an employee at IO Biotech ApS. The other authors declare “no conflict of interest”.

Data availability statement

The data that support the findings of this study are available from the corresponding author, MHA, upon reasonable request.

Supplementary material

Supplemental data for this article can be accessed online at https://doi.org/10.1080/2162402X.2024.2318053.

Additional information

Funding

The work was supported by the National Center for Cancer Immune Therapy, CCIT-DK.