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NCRs and DNAM-1 mediate NK cell recognition and lysis of human and mouse melanoma cell lines in vitro and in vivo
Open accessAbstract
NK cells use a variety of receptors to detect abnormal cells, including tumors and their metastases. However, in the case of melanoma, it remains to be determined what specific molecular interactions are involved and whether NK cells control metastatic progression and/or the route of dissemination. Here we show that human melanoma cell lines derived from LN metastases express ligands for natural cytotoxicity receptors (NCRs) and DNAX accessory molecule-1 (DNAM-1), two emerging NK cell receptors key for cancer cell recognition, but not NK group 2 member D (NKG2D). Compared with cell lines derived from metastases taken from other anatomical sites, LN metastases were more susceptible to NK cell lysis and preferentially targeted by adoptively transferred NK cells in a xenogeneic model of cell therapy. In mice, DNAM-1 and NCR ligands were also found on spontaneous melanomas and melanoma cell lines. Interference with DNAM-1 and NCRs by antibody blockade or genetic disruption reduced killing of melanoma cells. Taken together, these results show that DNAM-1 and NCRs are critical for NK cell-mediated innate immunity to melanoma cells and provide a background to design NK cell-based immunotherapeutic strategies against melanoma and possibly other tumors.
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“Moreover, NKp30, NKp46, and DNAM-1 are NK activation receptors involved in the recognition and lysis of different tumors, such as hematological malignancies [82], melanoma [83], and ovarian cancer [84].”
From Immunosenescence: a key player in cancer development (2020) · cites this paper as [83]
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Metadata
- Authors
- Lakshmikanth, T., Burke, S., Ali, T. H., Kimpfler, S., Ursini, F., Ruggeri, L., Capanni, M., Umansky, V., Paschen, A., Sucker, A., Pende, D., Groh, V., Biassoni, R., Höglund, P., Kato, M., Shibuya, K., Schadendorf, D., Anichini, A., Ferrone, S., Velardi, A., Kärre, K., Shibuya, A., Carbone, E., & Colucci, F.
- Affiliations
- Magna Graecia University (IT)
- Babraham Institute (GB)
- Heidelberg University (DE)
- University of Perugia (IT)
- Ospedale Policlinico San Martino (IT)
- Fred Hutch Cancer Center (US)
- Istituto Giannina Gaslini (IT)
- Karolinska Institutet (SE)
- Chubu University (JP)
- University of Tsukuba (JP)
- Fondazione IRCCS Istituto Nazionale dei Tumori (IT)
- University of Pittsburgh (US)
- ORCID
- Lakshmikanth, Tadepally
- Burke, Shannon
- Ali, Talib Hassan
- Ursini, Francesco
- Ruggeri, Loredana
- Umansky, Viktor
- Paschen, Annette
- Sucker, Antje
- Pende, Daniela
- Biassoni, Roberto
- Höglund, Petter
- Kato, Masashi
- Shibuya, Kazuko
- Schadendorf, Dirk
- Anichini, Andrea
- Ferrone, Soldano
- Velardi, Andrea
- Kärre, Klas
- Shibuya, Akira
- Carbone, Ennio
- Colucci, Francesco
- Venue
- Journal of Clinical Investigation
- Published
- 2009-05-01
- Volume
- 119
- Issue
- 5
- Pages
- 1251-1263
- ISSN
- 0021-9738 (ISSN-L)
- PMC
- PMC2673866
- OpenAlex
- W2143731593
- Cited by
- 347
- References
- 40
- Citations by year
- 2026: 4 · 2025: 9 · 2024: 10 · 2023: 14 · 2022: 14 · 2021: 24 · 2020: 29 · 2019: 31 · 2018: 15 · 2017: 24 · 2016: 26 · 2015: 26 · 2014: 27 · 2013: 23 · 2012: 25
- FWCI
- 10.21
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Journal of Clinical Investigation (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Archivio istituzionale della ricerca (Alma Mater Studiorum Università di Bologna) (submittedVersion)
- Archivio Istituzionale della Ricerca - Università degli Studi della Campania "Luigi Vanvitelli" (submittedVersion)
- Institutional Research Information System University of Ferrara (University of Ferrara) (submittedVersion)
- Funders
- Cancerfonden
- Karolinska Institutet
- Vetenskapsrådet
- Associazione Italiana per la Ricerca sul Cancro
- Medical Research Council
- Biotechnology and Biological Sciences Research Council (BBS/E/B/00001212, BBS/E/B/0000C212)
- National Cancer Institute (R01CA110249)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Immune Cell Function and Interaction
- Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
- Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
- Keywords
- natural killer cells, natural cytotoxicity receptors, DNAM-1, melanoma, lymph node metastasis, NK cell-mediated lysis, NK cell receptors, NKG2D, innate immunity, NK cell therapy, antibody blocking, adoptive NK cell transfer, tumor recognition
- MeSH terms
- T Lineage-Specific Activation Antigen 1, Animals, Antibodies, Antigens, Differentiation, T-Lymphocyte, Antigens, Ly, Cytotoxicity Tests, Immunologic, Cytotoxicity, Immunologic, DNA-Binding Proteins, Humans, Killer Cells, Natural, Ligands, Lymphatic Metastasis, Melanoma, Melanoma, Experimental, Mice, Inbred Strains, Mice, Transgenic, Lymphocyte Function-Associated Antigen-1, Immunotherapy, Adoptive, Mice, SCID, Mice, Inbred NOD, Mice, Knockout, Xenograft Model Antitumor Assays, Cell Line, Tumor, Mice, Interleukin Receptor Common gamma Subunit, Natural Killer T-Cells, Natural Cytotoxicity Triggering Receptor 1, Receptors, Natural Cytotoxicity Triggering
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