NK Cells, Tumor Cell Transition, and Tumor Progression in Solid Malignancies: New Hints for NK-Based Immunotherapy?
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.
Department of Experimental Medicine (DIMES), University of Genoa, 16132 Genova, Italy; Center of Excellence for Biomedical Research (CEBR), University of Genoa, 16132 Genova, Italy; Istituto Giannina Gaslini, 16147 Genova, Italy.
Claudia
0000-0001-6471-1424
C
Cantoni
IRCCS AOU San Martino-IST, 16132 Genova, Italy.
Leticia
L
Huergo-Zapico
IRCCS AOU San Martino-IST, 16132 Genova, Italy.
Monica
M
Parodi
Department of Experimental Medicine (DIMES), University of Genoa, 16132 Genova, Italy.
Marco
M
Pedrazzi
Department of Experimental Medicine (DIMES), University of Genoa, 16132 Genova, Italy; Center of Excellence for Biomedical Research (CEBR), University of Genoa, 16132 Genova, Italy; IRCCS AOU San Martino-IST, 16132 Genova, Italy.
Maria Cristina
MC
Mingari
Department of Experimental Medicine (DIMES), University of Genoa, 16132 Genova, Italy; Center of Excellence for Biomedical Research (CEBR), University of Genoa, 16132 Genova, Italy.
Alessandro
0000-0002-7116-426X
A
Moretta
Department of Experimental Medicine (DIMES), University of Genoa, 16132 Genova, Italy; Center of Excellence for Biomedical Research (CEBR), University of Genoa, 16132 Genova, Italy.
Bianca
B
Sparatore
Department of Functional Biology, IUOPA, University of Oviedo, 33006 Oviedo, Spain.
Segundo
S
Gonzalez
U1068, CRCM, Immunity and Cancer, INSERM, 1312 Marseille, France.
Daniel
D
Olive
Department of Experimental Medicine (DIMES), University of Genoa, 16132 Genova, Italy; Istituto Giannina Gaslini, 16147 Genova, Italy.
Cristina
C
Bottino
Department of Experimental Medicine (DIMES), University of Genoa, 16132 Genova, Italy; Center of Excellence for Biomedical Research (CEBR), University of Genoa, 16132 Genova, Italy.
Roberta
0000-0003-2806-1115
R
Castriconi
IRCCS AOU San Martino-IST, 16132 Genova, Italy.
Massimo
0000-0001-5372-7885
M
Vitale
D000818:Animals; D060890:B7-H1 Antigen / Q000378:metabolism; D003602:Cytotoxicity, Immunologic; D018450:Disease Progression; D058750:Epithelial-Mesenchymal Transition / Q000276:immunology; D006680:HLA Antigens / Q000378:metabolism; D024243:HMGB1 Protein / Q000502:physiology; D006801:Humans; D007108:Immune Tolerance; D007167:Immunotherapy; D007694:Killer Cells, Natural / Q000737:chemistry / Q000276:immunology*; D055655:NK Cell Lectin-Like Receptor Subfamily K / Q000378:metabolism; D009362:Neoplasm Metastasis / Q000517:prevention & control; D009369:Neoplasms / Q000276:immunology* / Q000503:physiopathology / Q000628:therapy*; D059016:Tumor Microenvironment / Q000276:immunology
D060890:B7-H1 Antigen; C423236:CD274 protein, human; D006680:HLA Antigens; D024243:HMGB1 Protein; C585491:HMGB1 protein, human; C527085:KLRK1 protein, human; D055655:NK Cell Lectin-Like Receptor Subfamily K