Doctoral thesis
Open access

Arginase 2 as a metabolic immune checkpoint in anti-tumor immunity

DirectorsReith, Walter
Defense date2019-03-21

Arginine depletion, an essential amino acid for T cells, is a major immunosuppressive mechanism for anti-tumoral T cells. Despite extensive characterisation of extracellular arginine depletion by the arginase enzyme Arg1, the role of the more ancestral Arg2 isoform in immunity, and especially in anti-tumor immunity, remained unaddressed. Preclinical murine melanoma and colorectal carcinoma models showed that, while Arg2-overexpression in tumor cells impaired adaptive anti-tumor responses, germ-line and CD8+ T cell-specific Arg2 deletion enhanced anti-tumor immune responses, reducing tumor growth. Notably, combination of Arg2 deletion and PD-1 blockade synergistically improved single-immunotherapy effects. Concomitantly, we also engineered a new mouse strain (Arg2em1Wreith), a tool for further comprehension of Arg2 post-transcriptional regulation by the immunorelevant microRNA-155. In conjunction with incipient data on human ARG2 inhibition in T cells, this thesis proposes Arg2 as a new molecular target for the improvement of T cell-based immunotherapies, at the forefront of cancer treatments in modern medicine.

  • Immunology
  • Tumor
  • Cancer
  • Arginine
  • Arginase
  • Immunometabolism
  • Immunotherapy
  • CD8 T cells
  • Anti-tumor
  • PD-1
  • Arg2
  • Arginase 2
  • Arg-II
Citation (ISO format)
MARTI LINDEZ, Adria-Arnau. Arginase 2 as a metabolic immune checkpoint in anti-tumor immunity. 2019. doi: 10.13097/archive-ouverte/unige:118259
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Technical informations

Creation05/17/2019 8:34:00 AM
First validation05/17/2019 8:34:00 AM
Update time03/15/2023 5:10:35 PM
Status update03/15/2023 5:10:34 PM
Last indexation09/18/2023 9:14:05 PM
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