Cancer-Initiating Cells from Colorectal cancer Patients Escape from T Cell-Mediated Immunosurveillance In Vitro through Membrane-Bound IL-4

Matilde Todaro, Giorgio Stassi, Tiziano Di Tomaso, Luca Ghirardelli, Michela Spinelli, Massimiliano Bissolati, Andrea Volonté, Michela Spinelli, Francesca Sanvito, Luca Albarello, Giorgio Parmiani, Giorgio Parmiani, Cristina Maccalli, Elena Orsenigo, Giorgio Stassi, Paolo Dellabona, Claudio Doglioni, Carlo Staudacher, Matilde Todaro, Giorgio ParmianiSoldano Ferrone

Risultato della ricerca: Articlepeer review

84 Citazioni (Scopus)


Cancer-initiating cells (CICs) that are responsible for tumor initiation, propagation, and resistance to standard therapies have been isolated from human solid tumors, including colorectal cancer (CRC). The aim of this study was to obtain an immunological profile of CRC-derived CICs and to identify CIC-associated target molecules for T cell immunotherapy. We have isolated cells with CIC properties along with their putative non-CIC autologous counterparts from human primary CRC tissues. These CICs have been shown to display “tumor-initiating/stemness” properties, including the expression of CIC-associated markers (e.g., CD44, CD24, ALDH-1, EpCAM, Lgr5), multipotency, and tumorigenicity following injection in immunodeficient mice. The immune profile of these cells was assessed by phenotype analysis and by in vitro stimulation of PBMCs with CICs as a source of Ags. CICs, compared with non-CIC counterparts, showed weak immunogenicity. This feature correlated with the expression of high levels of immu- nomodulatory molecules, such as IL-4, and with CIC-mediated inhibitory activity for anti-tumor T cell responses. CIC-associated IL-4 was found to be responsible for this negative function, which requires cell-to-cell contact with T lymphocytes and which is impaired by blocking IL-4 signaling. In addition, the CRC-associated Ag COA-1 was found to be expressed by CICs and to represent, in an autologous setting, a target molecule for anti-tumor T cells. Our study provides relevant information that may contribute to designing new immunotherapy protocols to target CICs in CRC patients
Lingua originaleEnglish
pagine (da-a)523-532
Numero di pagine10
RivistaJournal of Immunology
Stato di pubblicazionePublished - 2013

All Science Journal Classification (ASJC) codes

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