TY - JOUR
T1 - Human NK cells selective targeting of colon cancer-initiating cells
T2 - A role for natural cytotoxicity receptors and MHC class i molecules
AU - Tallerico, Rossana
AU - Todaro, Matilde
AU - Di Franco, Simone
AU - MacCalli, Cristina
AU - Garofalo, Cinzia
AU - Sottile, Rosa
AU - Palmieri, Camillo
AU - Tirinato, Luca
AU - Pangigadde, Pradeepa N.
AU - La Rocca, Rosanna
AU - Mandelboim, Ofer
AU - Stassi, Giorgio
AU - Di Fabrizio, Enzo
AU - Parmiani, Giorgio
AU - Moretta, Alessandro
AU - Dieli, Francesco
AU - Kärre, Klas
AU - Carbone, Ennio
PY - 2013/3/1
Y1 - 2013/3/1
N2 - Tumor cell populations have been recently proposed to be composed of two compartments: tumor-initiating cells characterized by a slow and asymmetrical growth, and the "differentiated" cancer cells with a fast and symmetrical growth. Cancer stem cells or cancer-initiating cells (CICs) play a crucial role in tumor recurrence. The resistance of CICs to drugs and irradiation often allows them to survive traditional therapy. NK cells are potent cytotoxic lymphocytes that can recognize tumor cells. In this study, we have analyzed the NK cell recognition of tumor target cells derived from the two cancer cell compartments of colon adenocarcinoma lesions. Our data demonstrate that freshly purified allogeneic NK cells can recognize and kill colorectal carcinoma- derived CICs whereas the non-CIC counterpart of the tumors (differentiated tumor cells), either autologous or allogeneic, is less susceptible to NK cells. This difference in the NK cell susceptibility correlates with higher expression on CICs of ligands for NKp30 and NKp44 in the natural cytotoxicity receptor (NCR) group of activating NK receptors. In contrast, CICs express lower levels of MHC class I, known to inhibit NK recognition, on their surface than do the "differentiated" tumor cells. These data have been validated by confocal microscopy where NCR ligands and MHC class I molecule membrane distribution have been analyzed. Moreover, NK cell receptor blockade in cytotoxicity assays demonstrates that NCRs play a major role in the recognition of CIC targets. This study strengthens the idea that biology-based therapy harnessing NK cells could be an attractive opportunity in solid tumors.
AB - Tumor cell populations have been recently proposed to be composed of two compartments: tumor-initiating cells characterized by a slow and asymmetrical growth, and the "differentiated" cancer cells with a fast and symmetrical growth. Cancer stem cells or cancer-initiating cells (CICs) play a crucial role in tumor recurrence. The resistance of CICs to drugs and irradiation often allows them to survive traditional therapy. NK cells are potent cytotoxic lymphocytes that can recognize tumor cells. In this study, we have analyzed the NK cell recognition of tumor target cells derived from the two cancer cell compartments of colon adenocarcinoma lesions. Our data demonstrate that freshly purified allogeneic NK cells can recognize and kill colorectal carcinoma- derived CICs whereas the non-CIC counterpart of the tumors (differentiated tumor cells), either autologous or allogeneic, is less susceptible to NK cells. This difference in the NK cell susceptibility correlates with higher expression on CICs of ligands for NKp30 and NKp44 in the natural cytotoxicity receptor (NCR) group of activating NK receptors. In contrast, CICs express lower levels of MHC class I, known to inhibit NK recognition, on their surface than do the "differentiated" tumor cells. These data have been validated by confocal microscopy where NCR ligands and MHC class I molecule membrane distribution have been analyzed. Moreover, NK cell receptor blockade in cytotoxicity assays demonstrates that NCRs play a major role in the recognition of CIC targets. This study strengthens the idea that biology-based therapy harnessing NK cells could be an attractive opportunity in solid tumors.
UR - http://www.scopus.com/inward/record.url?scp=84874260704&partnerID=8YFLogxK
U2 - 10.4049/jimmunol.1201542
DO - 10.4049/jimmunol.1201542
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C2 - 23345327
AN - SCOPUS:84874260704
SN - 0022-1767
VL - 190
SP - 2381
EP - 2390
JO - Journal of Immunology
JF - Journal of Immunology
IS - 5
ER -