Cited by 234Immune Cell Function and InteractionImmunotherapy and Immune ResponsesReproductive System and Pregnancy

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DNAX Accessory Molecule-1 Mediated Recognition of Freshly Isolated Ovarian Carcinoma by Resting Natural Killer Cells

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Carlsten, Mattias, Björkström, Niklas K., Norell, Håkan, Bryceson, Yenan, van Hall, Thorbald, Baumann, Bettina C., Hanson, Mikael, Schedvins, Kjell, Kiessling, Rolf, Ljunggren, Hans-Gustaf, Malmberg, Karl-Johan·2007·Cancer Research

DOI 10.1158/0008-5472.can-06-2264

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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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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)
ORCID: Carlsten, Mattias
Bryceson, Yenan
Kiessling, Rolf
Ljunggren, Hans-Gustaf
Malmberg, Karl-Johan
Venue: Cancer Research
Publisher: American Association for Cancer Research (AACR)
Published: 2007-02-01
Volume: 67
Issue: 3
Pages: 1317-1325
ISSN: 0008-5472 (ISSN-L)
1538-7445
DOI: 10.1158/0008-5472.can-06-2264
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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DNAX Accessory Molecule-1 Mediated Recognition of Freshly Isolated Ovarian Carcinoma by Resting Natural Killer Cells

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