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

Abstract

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.

• Authors: Claudia Cantoni, Leticia Huergo-Zapico, Monica Parodi, Marco Pedrazzi, Maria Cristina Mingari, Alessandro Moretta, Bianca Sparatore, Segundo Gonzalez, Daniel Olive, Cristina Bottino, Roberta Castriconi, Massimo Vitale
• Journal: Journal of immunology research (J Immunol Res) Vol. 2016 Pg. 4684268 ( 2016) ISSN: 2314-7156 [Electronic] Egypt
• PMID: 27294158 (Publication Type: Journal Article, Review)

Chemical References

• B7-H1 Antigen
• CD274 protein, human
• HLA Antigens
• HMGB1 Protein
• HMGB1 protein, human
• KLRK1 protein, human
• NK Cell Lectin-Like Receptor Subfamily K

Topics

• Animals
• B7-H1 Antigen (metabolism)
• Cytotoxicity, Immunologic
• Disease Progression
• Epithelial-Mesenchymal Transition (immunology)
• HLA Antigens (metabolism)
• HMGB1 Protein (physiology)
• Humans
• Immune Tolerance
• Immunotherapy
• Killer Cells, Natural (chemistry, immunology)
• NK Cell Lectin-Like Receptor Subfamily K (metabolism)
• Neoplasm Metastasis (prevention & control)
• Neoplasms (immunology, physiopathology, therapy)
• Tumor Microenvironment (immunology)