Human NK cells selective targeting of colon cancer-initiating cells

A role for natural cytotoxicity receptors and MHC class i molecules

Rossana Tallerico, Matilde Todaro, Simone Di Franco, Cristina Maccalli, Cinzia Garofalo, Rosa Sottile, Camillo Palmieri, Luca Tirinato, Pradeepa N. Pangigadde, Rosanna La Rocca, Ofer Mandelboim, Giorgio Stassi, Enzo Di Fabrizio, Giorgio Parmiani, Alessandro Moretta, Francesco Dieli, Klas Kärre, Ennio Carbone

Research output: Contribution to journalArticle

102 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)2381-2390
Number of pages10
JournalJournal of Immunology
Volume190
Issue number5
DOIs
Publication statusPublished - 1 Mar 2013
Externally publishedYes

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Natural Killer Cells
Colonic Neoplasms
Neoplasms
Neoplastic Stem Cells
Natural Killer Cell Receptors
Ligands
Growth
Confocal Microscopy
Colorectal Neoplasms
Colon
Adenocarcinoma

ASJC Scopus subject areas

  • Immunology

Cite this

Human NK cells selective targeting of colon cancer-initiating cells : A role for natural cytotoxicity receptors and MHC class i molecules. / Tallerico, Rossana; Todaro, Matilde; Di Franco, Simone; Maccalli, Cristina; Garofalo, Cinzia; Sottile, Rosa; Palmieri, Camillo; Tirinato, Luca; Pangigadde, Pradeepa N.; La Rocca, Rosanna; Mandelboim, Ofer; Stassi, Giorgio; Di Fabrizio, Enzo; Parmiani, Giorgio; Moretta, Alessandro; Dieli, Francesco; Kärre, Klas; Carbone, Ennio.

In: Journal of Immunology, Vol. 190, No. 5, 01.03.2013, p. 2381-2390.

Research output: Contribution to journalArticle

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 2013, 'Human NK cells selective targeting of colon cancer-initiating cells: A role for natural cytotoxicity receptors and MHC class i molecules', Journal of Immunology, vol. 190, no. 5, pp. 2381-2390. https://doi.org/10.4049/jimmunol.1201542
Tallerico, Rossana ; Todaro, Matilde ; Di Franco, Simone ; Maccalli, Cristina ; Garofalo, Cinzia ; Sottile, Rosa ; Palmieri, Camillo ; Tirinato, Luca ; Pangigadde, Pradeepa N. ; La Rocca, Rosanna ; Mandelboim, Ofer ; Stassi, Giorgio ; Di Fabrizio, Enzo ; Parmiani, Giorgio ; Moretta, Alessandro ; Dieli, Francesco ; Kärre, Klas ; Carbone, Ennio. / Human NK cells selective targeting of colon cancer-initiating cells : A role for natural cytotoxicity receptors and MHC class i molecules. In: Journal of Immunology. 2013 ; Vol. 190, No. 5. pp. 2381-2390.
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AU - Maccalli, Cristina

AU - Garofalo, Cinzia

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AU - Palmieri, Camillo

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AU - Pangigadde, Pradeepa N.

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AU - Stassi, Giorgio

AU - Di Fabrizio, Enzo

AU - Parmiani, Giorgio

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