Details

Autor(en) / Beteiligte

• Mantovani, Stefania
• Varchetta, Stefania
• Mele, Dalila
• Maiello, Roberta
• Donadon, Matteo
• Soldani, Cristiana
• Franceschini, Barbara
• Torzilli, Guido
• Tartaglia, Giuseppe
• Maestri, Marcello
• Piccolo, Gaetano
• Barabino, Matteo
• Opocher, Enrico
• Bernuzzi, Stefano
• Mondelli, Mario U
• Oliviero, Barbara

Titel

Defective DNAM-1 Dependent Cytotoxicity in Hepatocellular Carcinoma-Infiltrating NK Cells

Ist Teil von

• Cancers, 2022-08, Vol.14 (16), p.4060

Ort / Verlag

Basel: MDPI AG

Erscheinungsjahr

2022

Link zum Volltext

Quelle

EZB Electronic Journals Library

Beschreibungen/Notizen

• 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.