ArticleHaematologica2021
PVRIG is a novel natural killer cell immune checkpoint receptor in acute myeloid leukemia
Article in Haematologica, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 33 citations in OpenAlex.
- Identification and validation of blood leukocyte DNA methylation biomarkers for early detection of colorectal neoplasm.Chinese medical journal · 2026Article
- Expression of the TIGIT axis and the CD39/CD73 purinergic pathway in bone metastasis-derived immune cells.Cancer immunology, immunotherapy : CII · 2025Article
- Natural Killer Cell Immune Checkpoints and Their Therapeutic Targeting in Cancer Treatment.Research (Washington, D.C.) · 2025Article
- Unlocking the therapeutic potential of the NKG2A-HLA-E immune checkpoint pathway in T cells and NK cells for cancer immunotherapy.Journal for immunotherapy of cancer · 2024Review
- Advances and clinical applications of immune checkpoint inhibitors in hematological malignancies.Cancer communications (London, England) · 2024Review
- PVRL2 Suppresses Antitumor Immunity through PVRIG- and TIGIT-independent Pathways.Cancer immunology research · 2024Article
- The role of exhausted natural killer cells in the immunopathogenesis and treatment of leukemia.Cell communication and signaling : CCS · 2024Review
- The Nectin family ligands, PVRL2 and PVR, in cancer immunology and immunotherapy.Frontiers in immunology · 2024Review
- Host immunity associated with spontaneous suppression of viremia in therapy-naïve young rhesus macaques following neonatal SHIV infection.Journal of virology · 2023Article
- LEF1 Drives a Central Memory Program and Supports Antitumor Activity of Natural Killer T Cells.Cancer immunology research · 2023Article
- A potential area of use for immune checkpoint inhibitors: Targeting bone marrow microenvironment in acute myeloid leukemia.Frontiers in immunology · 2023Review
- Harnessing natural killer cells for cancer immunotherapy: dispatching the first responders.Nature reviews. Drug discovery · 2022Review
- Blockade of novel immune checkpoints and new therapeutic combinations to boost antitumor immunity.Journal of experimental & clinical cancer research : CR · 2022Review
- Overcoming tumor resistance mechanisms in CAR-NK cell therapy.Frontiers in immunology · 2022Review
- Combined Blockade of TIGIT and CD39 or A2AR Enhances NK-92 Cell-Mediated Cytotoxicity in AML.International journal of molecular sciences · 2021Article
- The CD112R/CD112 axis: a breakthrough in cancer immunotherapy.Journal of experimental & clinical cancer research : CR · 2021Review
- Blockade of checkpoint receptor PVRIG unleashes anti-tumor immunity of NK cells in murine and human solid tumors.Journal of hematology & oncology · 2021Article
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
This study explored the novel immune checkpoint poliovirus receptor-related immunoglobulin domain-containing (PVRIG) in acute myeloid leukemia (AML). We showed that AML patient blasts consistently expressed the PVRIG ligand (poliovirus receptor-related 2, PVRL2). Furthermore, PVRIG blockade significantly enhanced NK cell killing of PVRL2+, poliovirus receptor (PVR)lo AML cell lines, and significantly increased NK cell activation and degranulation in the context of patient primary AML blasts. However, in AML patient bone marrow, NK cell PVRIG expression levels were not increased. To understand how PVRIG blockade might potentially be exploited therapeutically, we investigated the biology of PVRIG and revealed that NK cell activation resulted in reduced PVRIG expression on the cell surface. This occurred whether NK cells were activated by tumour cell recognition, cytokines (IL-2 and IL-12) or activating receptor stimulation (CD16 and NKp46). PVRIG was present at higher levels in the cytoplasm than on the cell surface, particularly on CD56bright NK cells, which further increased cytoplasmic PVRIG levels following IL-2 and IL-12 activation. PVRIG was continually transported to the cell surface via the endoplasmic reticulum (ER) and Golgi in both unstimulated and activated NK cells. Taken together, our findings suggest that anti- PVRIG blocking antibody functions by binding to surface-bound PVRIG, which undergoes rapid turnover in both unstimulated and activated NK cells. We conclude that the PVRIGPVRL2 immune checkpoint axis can feasibly be targeted with PVRIG blocking antibody for NK-mediated immunotherapy of PVRL2+ AML.
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