ArticleProceedings of the National Academy of Sciences of the United States of America2009
Genetic and antibody-mediated reprogramming of natural killer cell missing-self recognition in vivo.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.
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Who cites it
43 citing papers in PubMed, 65 citations in OpenAlex.
- Checkpoint Inhibition of KIR2D with the Monoclonal Antibody IPH2101 Induces Contraction and Hyporesponsiveness of NK Cells in Patients with Myeloma.Clinical cancer research : an official journal of the American Association for Cancer Research · 2016Trial
- Addressing the challenges of immunogenicity, heterogeneity and tumorigenicity in the clinical translation of human embryonic stem cells.Stem cell research & therapy · 2025Review
- Review
- Targeting Potential of Innate Lymphoid Cells in Melanoma and Other Cancers.Pharmaceutics · 2023Review
- Article
- The SIRPα-CD47 immune checkpoint in NK cells.The Journal of experimental medicine · 2021Article
- Natural Born Killers: NK Cells in Cancer Therapy.Cancers · 2020Review
- Review
- Are Conventional Type 1 Dendritic Cells Critical for Protective Antitumor Immunity and How?Frontiers in immunology · 2019Review
- CIMT 2017: Anniversary symposium - Report on the 15th CIMT Annual Meeting of the Association for Cancer Immunotherapy.Human vaccines & immunotherapeutics · 2017Article
- Regulation of mTOR, Metabolic Fitness, and Effector Functions by Cytokines in Natural Killer Cells.Cancers · 2017Review
- NK cell education via nonclassical MHC and non-MHC ligands.Cellular & molecular immunology · 2017Review
- Patient's Natural Killer Cells in the Era of Targeted Therapies: Role for Tumor Killers.Frontiers in immunology · 2017Article
- Mouse models in oncoimmunology.Nature reviews. Cancer · 2016Review
- Effects of anti-NKG2A antibody administration on leukemia and normal hematopoietic cells.Haematologica · 2016Article
- Killer-cell Immunoglobulin-like Receptor (KIR) gene profiles modify HIV disease course, not HIV acquisition in South African women.BMC infectious diseases · 2016Article
- Underground Adaptation to a Hostile Environment: Acute Myeloid Leukemia vs. Natural Killer Cells.Frontiers in immunology · 2016Review
- Epigenetic suppression of the antitumor cytotoxicity of NK cells by histone deacetylase inhibitor valproic acid.American journal of cancer research · 2016Article
- NK Cell and CD4+FoxP3+ Regulatory T Cell Based Therapies for Hematopoietic Stem Cell Engraftment.Stem cells international · 2016Review
- Therapeutic approaches to enhance natural killer cell cytotoxicity against cancer: the force awakens.Nature reviews. Drug discovery · 2015Review
Corrections and comments
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Authors and funding
10 authors at 5 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Natural killer (NK) cells are lymphocytes of the innate immune system able to recognize and kill tumors lacking self-MHC class I molecules. This "missing-self" recognition is mediated by the lack of engagement of MHC class I-specific inhibitory NK cell receptors that include the killer cell Ig-like receptors (KIR) in humans and Ly49 molecules in mice. A promising immunotherapeutic strategy against MHC class I(+) cancer cells is to block NK cell inhibitory receptors using monoclonal antibodies (mAb). However, interactions between MHC class I molecules and their inhibitory receptors are also required for the acquisition of NK cell functional competence, a process referred as to "education." In addition, inhibitory receptors are involved in self-tolerance on educated NK cells. Here, we developed a preclinical mouse model in which all NK cells are educated by a single transgenic inhibitory receptor, human KIR2DL3, through the engagement with its HLA-Cw3 ligand. This approach revealed that NK cells could be reprogrammed to control the development of mouse syngenic tumors in vivo. Moreover, in vivo anti-KIR mAb treatment induced the killing of HLA(+) target cells without breaking self-tolerance. Finally, the long-term infusion of anti-KIR mAb neither abolished NK cell education nor tumor cell recognition. Therefore, these results strongly support the use of inhibitory receptor blockade in cancer patients.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.