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Journal of Immunology Research
Volume 2016 (2016), Article ID 4684268, 13 pages
Review Article

NK Cells, Tumor Cell Transition, and Tumor Progression in Solid Malignancies: New Hints for NK-Based Immunotherapy?

1Department of Experimental Medicine (DIMES), University of Genoa, 16132 Genova, Italy
2Center of Excellence for Biomedical Research (CEBR), University of Genoa, 16132 Genova, Italy
3Istituto Giannina Gaslini, 16147 Genova, Italy
4IRCCS AOU San Martino-IST, 16132 Genova, Italy
5Department of Functional Biology, IUOPA, University of Oviedo, 33006 Oviedo, Spain
6U1068, CRCM, Immunity and Cancer, INSERM, 1312 Marseille, France

Received 2 November 2015; Accepted 10 April 2016

Academic Editor: Stuart Berzins

Copyright © 2016 Claudia Cantoni et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


Several evidences suggest that NK cells can patrol the body and eliminate tumors in their initial phases but may hardly control established solid tumors. Multiple factors, including the transition of tumor cells towards a proinvasive/prometastatic phenotype, the immunosuppressive effect of the tumor microenvironment, and the tumor structure complexity, may account for limited NK cell efficacy. Several putative mechanisms of NK cell suppression have been defined in these last years; conversely, the cross talk between NK cells and tumor cells undergoing different transitional phases remains poorly explored. Nevertheless, recent in vitro studies and immunohistochemical analyses on tumor biopsies suggest that NK cells could not only kill tumor cells but also influence their evolution. Indeed, NK cells may induce tumor cells to change the expression of HLA-I, PD-L1, or NKG2D-L and modulate their susceptibility to the immune response. Moreover, NK cells may be preferentially located in the borders of tumor masses, where, indeed, tumor cells can undergo Epithelial-to-Mesenchymal Transition (EMT) acquiring prometastatic phenotype. Finally, the recently highlighted role of HMGB1 both in EMT and in amplifying the recruitment of NK cells provides further hints on a possible effect of NK cells on tumor progression and fosters new studies on this issue.