Human NK cells selective targeting of colon cancer-initiating cells: a role for natural cytotoxicity receptors and MHC class I molecules
| Autor: | Alessandro Moretta, Pradeepa N. Pangigadde, Cinzia Garofalo, Francesco Dieli, Rosa Sottile, Ofer Mandelboim, Giorgio Parmiani, Enzo Di Fabrizio, Luca Tirinato, Simone Di Franco, Rosanna La Rocca, Rossana Tallerico, Camillo Palmieri, Giorgio Stassi, Cristina Maccalli, Matilde Todaro, Ennio Carbone, Klas Kärre |
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| Přispěvatelé: | Tallerico, R, Todaro, M, Di Franco, S, Maccalli, C, Garofalo, C, Sottile, R, Palmieri, C, Tirinato, L, Pangigadde, PN, La Rocca, R, Mandelboim, O, Stassi, G, Di Fabrizio, E, Parmiani, G, Moretta, A, Dieli, F, Kärre, K, Carbone, E, Pangigadde, Pn |
| Jazyk: | angličtina |
| Rok vydání: | 2013 |
| Předmět: |
Cytotoxicity
Immunologic NK Immunology Gene Expression Cancer Stem Cell Mice SCID Biology Adenocarcinoma Interleukin 21 Mice NK-92 Cancer stem cell Mice Inbred NOD Tumor Cells Cultured Immunology and Allergy Cytotoxic T cell Animals Humans Cell Lineage Settore MED/04 - Patologia Generale Lymphokine-activated killer cell Microscopy Confocal Natural Cytotoxicity Triggering Receptor 3 Natural Cytotoxicity Triggering Receptor 2 Janus kinase 3 Histocompatibility Antigens Class I nessuna parola chiave Killer Cells Natural Organ Specificity Cancer cell Colonic Neoplasms Cancer research Interleukin 12 Neoplastic Stem Cells immunotherapy |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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