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DNAX Accessory Molecule-1 Mediated Recognition of Freshly Isolated Ovarian Carcinoma by Resting Natural Killer Cells
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Abstract
Although natural killer (NK) cells are well known for their ability to kill tumors, few studies have addressed the interactions between resting (nonactivated) NK cells and freshly isolated human tumors. Here, we show that human leukocyte antigen class Ilow tumor cells isolated directly from patients with advanced ovarian carcinoma trigger degranulation by resting allogeneic NK cells. This was paralleled by induction of granzyme B and caspase-6 activities in the tumor cells and significant tumor cell lysis. Ovarian carcinoma cells displayed ubiquitous expression of the DNAX accessory molecule-1 (DNAM-1) ligand PVR and sparse/heterogeneous expression of the NKG2D ligands MICA/MICB and ULBP1, ULBP2, and ULBP3. In line with the NK receptor ligand expression profiles, antibody-mediated blockade of activating receptor pathways revealed a dominant role for DNAM-1 and a complementary contribution of NKG2D signaling in tumor cell recognition. These results show that resting NK cells are capable of directly recognizing freshly isolated human tumor cells and identify ovarian carcinoma as a potential target for adoptive NK cell–based immunotherapy. [Cancer Res 2007;67(3):1317–25]
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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 [84]
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Metadata
- Authors
- Carlsten, M., Björkström, N. K., Norell, H., Bryceson, Y., van Hall, T., Baumann, B. C., Hanson, M., Schedvins, K., Kiessling, R., Ljunggren, H.-G., & Malmberg, K.-J.
- Affiliations
- Karolinska University Hospital (SE)
- 1Center for Infectious Medicine, Department of Medicine, Karolinska Institutet, Karolinska University Hospital Huddinge;
- 2Immune and Gene Therapy Laboratory, Cancer Center Karolinska, Department of Oncology and Pathology, Karolinska Institutet;
- Karolinska Institutet (SE)
- Venue
- Cancer Research
- Published
- 2007-02-01
- Volume
- 67
- Issue
- 3
- Pages
- 1317-1325
- ISSN
- 0008-5472 (ISSN-L)
- 1538-7445
- OpenAlex
- W2104794630
- Cited by
- 234
- References
- 40
- Citations by year
- 2026: 3 · 2025: 3 · 2024: 8 · 2023: 10 · 2022: 7 · 2021: 14 · 2020: 18 · 2019: 11 · 2018: 16 · 2017: 14 · 2016: 11 · 2015: 14 · 2014: 14 · 2013: 14 · 2012: 14
- FWCI
- 5.33
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Cancer Research (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Novartis Foundation
- Stiftelsen för Strategisk Forskning
- Cancerfonden
- Svenska Sällskapet för Medicinsk Forskning
- Karolinska Institutet
- Vetenskapsrådet
- National Institutes of Health
- National Cancer Institute (R01CA102280, CA 102280)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Immune Cell Function and Interaction
- Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
- Life Sciences › Immunology and Microbiology › Immunology › Reproductive System and Pregnancy
- Keywords
- DNAM-1, PVR, NKG2D, ovarian carcinoma, NK cell degranulation, granzyme B, caspase-6, ULBP, tumor cell lysis, NK cell therapy, cancer cell detection
- MeSH terms
- T Lineage-Specific Activation Antigen 1, Antigens, Differentiation, T-Lymphocyte, Female, Humans, Killer Cells, Natural, Ligands, Ovarian Neoplasms, Receptors, Immunologic, Cell Degranulation, K562 Cells, Granzymes, Receptors, Natural Killer Cell, NK Cell Lectin-Like Receptor Subfamily K
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