CD155 is an adhesion molecule belonging to the Nectin/Nectin-like family often overexpressed on tumor cells and involved in many different processes such as cell adhesion, migration and proliferation. In contrast to these pro-tumorigenic functions, CD155 is also a ligand for the activating receptor DNAM-1 expressed on cytotoxic lymphocytes including Natural Killer (NK) cells and involved in anti-tumor immune response. However, during tumor progression inhibitory receptors for CD155 are up-regulated on the surface of effector cells, contributing to an impairment of their cytotoxic capacity. In this review we will focus on the roles of CD155 as a ligand for the activating receptor DNAM-1 regulating immune surveillance against cancer and as pro-oncogenic molecule favoring tumor proliferation, invasion and immune evasion. A deeper understanding of the multiple roles played by CD155 in cancer development contributes to improving anti-tumor strategies aimed to potentiate immune response against cancer.

Ags. Studies are ongoing to compare nanovesicles derived from sera of atopic individuals before and during an acute phase of allergic reaction. Collectively, our data uncovered a new role for nanovesicles derived from activated MCs in the positive regulation of allergic responses, as depicted in our working model (Figure S6). Understanding how these nanovesicles influence the hypersensitivity reactions could help the development of more efficient therapies. ACK N OWLED G M ENTS This work was supported by the Italian Ministry of Education, Universities and Research-Dipartimenti di Eccellenza-L. 232/2016 and the Pasteur Institute-Cenci Bolognetti Foundation-Call 2012. EV is supported by a fellowship from AIRC (Associazione Italiana per la Ricerca sul Cancro). We are grateful to Dr J.-P. Kinet for generous access to anti-FcεRI β chain antibody and to Dr B. Wilson for helpful advices on exosome isolation. We thank Dr B. Zitti for isolating mouse bone marrow cells (mBMMCs), and Drs. G. Bernardini, F. Antonangeli, G. Sciumè and E. Sanseviero for technical advises on mBMMC culture. We also thank B. Milana for expert technical assistance, L. Simonelli for technical assistance in electron microscopy procedures and L. Cutini for IgE determination. The confocal fluorescence images were collected at the CLNS Imaging Facility of the Istituto Italiano di Tecnologia (Rome, Italy).

Nectin2 is a member of immunoglobulin-like cell adhesion molecules and plays a prominent role in the establishment of adherens and tight junctions. It is also upregulated on the surface of tumor and virus-infected cells where it functions as a ligand for the activating receptor CD226, thus contributing to cytotoxic lymphocyte-mediated recognition and killing of damaged cells.Little is currently known about the regulation of Nectin2 expression and, in particular, whether posttranscriptional and posttranslational mechanisms are involved. Here, we analyzed Nectin2 expression on a panel of human tumor cell lines and primary cultures and we found that Nectin2 is mainly expressed in cytoplasmic pools. Moreover, we demonstrated that ubiquitination of Nectin2 promotes its degradation and is responsible for protein intracellular retention. Indeed, inhibition of the ubiquitin pathway results in increased Nectin2 surface expression and enhances tumor cell susceptibility to NK cell cytotoxicity. Our results demonstrate a previously unknown mechanism of Nectin2 regulation revealing that the ubiquitin pathway represents a potential target of intervention in order to increase susceptibility to NK cell-mediated lysis.