DNAX accessory molecule-1 mediated recognition of freshly isolated ovarian carcinoma by resting natural killer cells
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 I(low) tumor cells isolated directly from patien...
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| Veröffentlicht in: | Cancer research (Chicago, Ill.) Ill.), 2007-02, Vol.67 (3), p.1317-1325 |
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| creator | CARLSTEN, Mattias BJORKSTRÖM, Niklas K MALMBERG, Karl-Johan NORELL, Hakan BRYCESON, Yenan VAN HALL, Thorbald BAUMANN, Bettina C HANSON, Mikael SCHEDVINS, Kjell KIESSLING, Rolf LJUNGGREN, Hans-Gustaf |
| description | 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 I(low) 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. |
| doi_str_mv | 10.1158/0008-5472.can-06-2264 |
| format | Article |
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Here, we show that human leukocyte antigen class I(low) 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.</description><identifier>ISSN: 0008-5472</identifier><identifier>EISSN: 1538-7445</identifier><identifier>DOI: 10.1158/0008-5472.can-06-2264</identifier><identifier>PMID: 17283169</identifier><identifier>CODEN: CNREA8</identifier><language>eng</language><publisher>Philadelphia, PA: American Association for Cancer Research</publisher><subject>Antigens, Differentiation, T-Lymphocyte - immunology ; Antineoplastic agents ; Biological and medical sciences ; Cell Degranulation - immunology ; Female ; Female genital diseases ; Granzymes - metabolism ; Gynecology. Andrology. Obstetrics ; Humans ; K562 Cells ; Killer Cells, Natural - immunology ; Ligands ; Medical sciences ; NK Cell Lectin-Like Receptor Subfamily K ; Ovarian Neoplasms - enzymology ; Ovarian Neoplasms - immunology ; Pharmacology. 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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.</description><subject>Antigens, Differentiation, T-Lymphocyte - immunology</subject><subject>Antineoplastic agents</subject><subject>Biological and medical sciences</subject><subject>Cell Degranulation - immunology</subject><subject>Female</subject><subject>Female genital diseases</subject><subject>Granzymes - metabolism</subject><subject>Gynecology. Andrology. Obstetrics</subject><subject>Humans</subject><subject>K562 Cells</subject><subject>Killer Cells, Natural - immunology</subject><subject>Ligands</subject><subject>Medical sciences</subject><subject>NK Cell Lectin-Like Receptor Subfamily K</subject><subject>Ovarian Neoplasms - enzymology</subject><subject>Ovarian Neoplasms - immunology</subject><subject>Pharmacology. 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| source | MEDLINE; Free E-Journal (出版社公開部分のみ）; Highwire Press American Association for Cancer Research - AACR Journals |
| subjects | Antigens, Differentiation, T-Lymphocyte - immunology Antineoplastic agents Biological and medical sciences Cell Degranulation - immunology Female Female genital diseases Granzymes - metabolism Gynecology. Andrology. Obstetrics Humans K562 Cells Killer Cells, Natural - immunology Ligands Medical sciences NK Cell Lectin-Like Receptor Subfamily K Ovarian Neoplasms - enzymology Ovarian Neoplasms - immunology Pharmacology. Drug treatments Receptors, Immunologic - immunology Receptors, Natural Killer Cell Tumors |
| title | DNAX accessory molecule-1 mediated recognition of freshly isolated ovarian carcinoma by resting natural killer cells |
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