“ [...] there is strong preclinical evidence that disruption of NKG2A interactions with HLA-E can stimulate both NK cell and cytotoxic T cell effector functions against cancer .”
BUFFALO, NY- August 21, 2024 – A new editorial was published in Oncotarget's Volume 15 on July 17, 2024, entitled, “ Strategies to disrupt NKG2A:HLA-E interactions for improved anti-cancer immunity .”
Two studies using CRISPR screens in cancer cells identified HLA-E as a critical negative regulator of NK cell interactions with cancer cells. Consistent with this, IFNγ signaling was associated with NK cell resistance due to increased STAT1 activation and enhanced HLA-E expression. This effect is also evident in the murine homolog of HLA-E, Qa-1b, which was upregulated by inflammatory signals across all cell types tested.
In addition to inflammatory signals, researchers Jack G. Fisher, Lara V. Graham, and Matthew D. Blunt from Clinical and Experimental Sciences, Faculty of Medicine at the University of Southampton, UK , recently demonstrated that surface expression of HLA-E is increased by lymph node-associated signals IL-4 and CD40L on primary chronic lymphocytic leukaemia (CLL) cells.
Additionally, two recent studies have shown that HLA-E can protect circulating tumor cells from NK cell lysis via NKG2A, suggesting that targeting the NKG2A axis could be a promising strategy for preventing metastasis in solid tumors.
“In conclusion, there is strong preclinical evidence that disruption of NKG2A interactions with HLA-E can stimulate both NK cell and cytotoxic T cell effector functions against cancer.”
Continue reading: DOI: https://doi.org/10.18632/oncotarget.28610
Correspondence to: Matthew D. Blunt - m.d.blunt@soton.ac.uk
Video short: https://www.youtube.com/watch?v=iQREIa-RToU
Keywords: Natural killer (NK) cells, immunotherapy, NKG2A, immune checkpoint blockade, HLA-E
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Strategies to disrupt NKG2A:HLA-E interactions for improved anti-cancer immunity
17-Jul-2024
M.D.B has received research funding from Karyopharm Therapeutics.