Ontology highlight
ABSTRACT: 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.
SUBMITTER: Mantovani S
PROVIDER: S-EPMC9406989 | biostudies-literature | 2022 Aug
REPOSITORIES: biostudies-literature
Mantovani Stefania S Varchetta Stefania S Mele Dalila D Maiello Roberta R Donadon Matteo M Soldani Cristiana C Franceschini Barbara B Torzilli Guido G Tartaglia Giuseppe G Maestri Marcello M Piccolo Gaetano G Barabino Matteo M Opocher Enrico E Bernuzzi Stefano S Mondelli Mario U MU Oliviero Barbara B
Cancers 20220822 16
<h4>Background</h4>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.<h4>Methods</h4>Soluble CD155 was measured by ELISA. CD155 expression wa ...[more]