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

精氨酸酶-1 特异性 CD8+ T 细胞对恶性和调节性髓系细胞有反应

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

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.

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