Defective DNAM-1 Dependent Cytotoxicity in Hepatocellular Carcinoma-Infiltrating NK Cells
BACKGROUND: Natural killer (NK) cells play a key role in immune surveillance and response to tumors, their function regulated by NK cell receptors and their ligands. The DNAM-1 activating receptor recognizes the CD155 molecule expressed in several tumor cells, such as hepatocellular carcinoma (HCC). This study aims to investigate the role of the DNAM-1/CD155 axis in mediating the NK cell response in patients with HCC.
METHODS: Soluble CD155 was measured by ELISA. CD155 expression was sought in HCC cells by immunohistochemistry, qPCR, and flow cytometry. DNAM-1 modulation in NK cells was evaluated in transwell experiments and by a siRNA-mediated knockdown. NK cell functions were examined by direct DNAM-1 triggering.
RESULTS: sCD155 was increased in sera from HCC patients and correlated with the parameters of an advanced disease. The expression of CD155 in HCC showed a positive trend toward better overall survival. DNAM-1 downmodulation was induced by CD155-expressing HCC cells, in agreement with lower DNAM-1 expressions in tumor-infiltrating NK (NK-TIL) cells. DNAM-1-mediated cytotoxicity was defective both in circulating NK cells and in NK-TIL of HCC patients.
CONCLUSIONS: We provide evidence of alterations in the DNAM-1/CD155 axis in HCC, suggesting a possible mechanism of tumor resistance to innate immune surveillance.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2022 |
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| Erschienen: |
2022 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:14 |
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| Enthalten in: |
Cancers - 14(2022), 16 vom: 22. Aug. |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Mantovani, Stefania [VerfasserIn] |
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| Links: |
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| Themen: |
DNAM-1 |
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| Anmerkungen: |
Date Revised 30.08.2022 published: Electronic Citation Status PubMed-not-MEDLINE |
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| doi: |
10.3390/cancers14164060 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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NLM345294459 |
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| 520 | |a BACKGROUND: Natural killer (NK) cells play a key role in immune surveillance and response to tumors, their function regulated by NK cell receptors and their ligands. The DNAM-1 activating receptor recognizes the CD155 molecule expressed in several tumor cells, such as hepatocellular carcinoma (HCC). This study aims to investigate the role of the DNAM-1/CD155 axis in mediating the NK cell response in patients with HCC | ||
| 520 | |a METHODS: Soluble CD155 was measured by ELISA. CD155 expression was sought in HCC cells by immunohistochemistry, qPCR, and flow cytometry. DNAM-1 modulation in NK cells was evaluated in transwell experiments and by a siRNA-mediated knockdown. NK cell functions were examined by direct DNAM-1 triggering | ||
| 520 | |a RESULTS: sCD155 was increased in sera from HCC patients and correlated with the parameters of an advanced disease. The expression of CD155 in HCC showed a positive trend toward better overall survival. DNAM-1 downmodulation was induced by CD155-expressing HCC cells, in agreement with lower DNAM-1 expressions in tumor-infiltrating NK (NK-TIL) cells. DNAM-1-mediated cytotoxicity was defective both in circulating NK cells and in NK-TIL of HCC patients | ||
| 520 | |a CONCLUSIONS: We provide evidence of alterations in the DNAM-1/CD155 axis in HCC, suggesting a possible mechanism of tumor resistance to innate immune surveillance | ||
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| 700 | 1 | |a Mele, Dalila |e verfasserin |4 aut | |
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| 700 | 1 | |a Donadon, Matteo |e verfasserin |4 aut | |
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| 700 | 1 | |a Franceschini, Barbara |e verfasserin |4 aut | |
| 700 | 1 | |a Torzilli, Guido |e verfasserin |4 aut | |
| 700 | 1 | |a Tartaglia, Giuseppe |e verfasserin |4 aut | |
| 700 | 1 | |a Maestri, Marcello |e verfasserin |4 aut | |
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| 700 | 1 | |a Opocher, Enrico |e verfasserin |4 aut | |
| 700 | 1 | |a Bernuzzi, Stefano |e verfasserin |4 aut | |
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| 700 | 1 | |a Oliviero, Barbara |e verfasserin |4 aut | |
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