Stavrou, Victoria, Fultang, Livingstone ORCID: 0000-0002-8215-6660, Booth, Sarah, De Simone, Daniele, Bartnik, Arekdiusz, Scarpa, Ugo, Gneo, Luciana, Panetti, Silvia, Potluri, Sandeep, Almowaled, Meaad et al (show 13 more authors)
(2023)
Invariant NKT cells metabolically adapt to the acute myeloid leukaemia environment.
Cancer immunology, immunotherapy : CII, 72 (3).
pp. 543-560.
Abstract
Acute myeloid leukaemia (AML) creates an immunosuppressive environment to conventional T cells through Arginase 2 (ARG2)-induced arginine depletion. We identify that AML blasts release the acute phase protein serum amyloid A (SAA), which acts in an autocrine manner to upregulate ARG2 expression and activity, and promote AML blast viability. Following in vitro cross-talk invariant natural killer T (iNKT) cells become activated, upregulate mitochondrial capacity, and release IFN-γ. iNKT retain their ability to proliferate and be activated despite the low arginine AML environment, due to the upregulation of Large Neutral Amino Acid Transporter-1 (LAT-1) and Argininosuccinate Synthetase 1 (ASS)-dependent amino acid pathways, resulting in AML cell death. T cell proliferation is restored in vitro and in vivo. The capacity of iNKT cells to restore antigen-specific T cell immunity was similarly demonstrated against myeloid-derived suppressor cells (MDSCs) in wild-type and Jα18<sup>-/-</sup> syngeneic lymphoma-bearing models in vivo. Thus, stimulation of iNKT cell activity has the potential as an immunotherapy against AML or as an adjunct to boost antigen-specific T cell immunotherapies in haematological or solid cancers.
Item Type: | Article |
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Uncontrolled Keywords: | Humans, Arginine, Cell Proliferation, Leukemia, Myeloid, Acute, Natural Killer T-Cells, Myeloid-Derived Suppressor Cells |
Divisions: | Faculty of Health and Life Sciences Faculty of Health and Life Sciences > Institute of Systems, Molecular and Integrative Biology |
Depositing User: | Symplectic Admin |
Date Deposited: | 31 Jan 2024 11:49 |
Last Modified: | 31 Jan 2024 11:49 |
DOI: | 10.1007/s00262-022-03268-4 |
Open Access URL: | https://doi.org/10.1007/s00262-022-03268-4 |
Related URLs: | |
URI: | https://livrepository.liverpool.ac.uk/id/eprint/3178214 |