Enzymatic depletion of adenosine to overcome resistance to immune checkpoint inhibitors in non-small cell lung cancer
نویسندگان
چکیده
Abstract Despite the remarkable outcome of immune checkpoint inhibitors (ICIs) in non-small cell lung cancer (NSCLC), a large number patients remain unresponsive to this therapy. A key factor unresponsiveness ICIs is intrinsic therapeutic resistance where monocytic myeloid-derived suppressor cells (M-MDSCs) contribute significantly via suppressing CD8 +T mediated anti-tumor response. Our results showed that tumor microenvironment (TME), derived PGE 2; prostaglandin directly induces CD73 (an ecto-nucleotidase converts AMP immunosuppressive adenosine) expression M-MDSCs; consequently, expressing M-MDSCs suppress T adenosine thus confer ICIs. In addition, we have shown depletion PEGylated Adenosine Deaminase (PEG-ADA) can reinvigorate cells, ultimately enhance immunity.
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ژورنال
عنوان ژورنال: Journal of Immunology
سال: 2023
ISSN: ['1550-6606', '0022-1767']
DOI: https://doi.org/10.4049/jimmunol.210.supp.230.14