Efficient killing of human colon cancer stem cells by gammadelta T lymphocytes

Francesco Dieli, Carmela La Mendola, Nadia Rosalia Caccamo, Matilde Todaro, Alfredo Salerno, Giorgio Stassi, Flora Iovino, Gaspare Gulotta, Serena Meraviglia, Maria Giovanna Francipane, Giorgio Stassi, Matilde Todaro, Flora Iovino, Maria Giovanna Francipane, Matilde D'Asaro, Valentina Orlando

Risultato della ricerca: Articlepeer review

200 Citazioni (Scopus)


Colon cancer comprises a small population of cancer stem cells (CSC) that is responsible for tumor maintenance and resistant to cancer therapies, possibly allowing for tumor recapitulation once treatment stops. We previously demonstrated that such chemoresistance is mediated by autocrine production of IL-4 through the up-regulation of antiapoptotic proteins. Several innate and adaptive immune effector cells allow for the recognition and destruction of cancer precursors before they constitute the tumor mass. However, cellular immune-based therapies have not been experimented yet in the population of CSCs. Here, we show that the bisphosphonate zoledronate sensitizes colon CSCs to Vγ9Vδ2 T cell cytotoxicity. Proliferation and production of cytokines (TNF-α and IFN-γ) and cytotoxic and apoptotic molecules (TRAIL and granzymes) were also induced after exposure of Vγ9Vδ2 T cells to sensitized targets. Vγ9Vδ2 T cell cytotoxicity was mediated by the granule exocytosis pathway and was highly dependent on isoprenoid production by of tumor cells. Moreover, CSCs recognition and killing was mainly TCR mediated, whereas NKG2D played a role only when tumor targets expressed several NKG2D ligands. We conclude that intentional activation of Vγ9Vδ2 T cells by zoledronate may substantially increase antitumor activities and represent a novel strategy for colon cancer immunotherapy.
Lingua originaleEnglish
pagine (da-a)7287-7296
Numero di pagine10
RivistaJournal of Immunology
Stato di pubblicazionePublished - 2009

All Science Journal Classification (ASJC) codes

  • ???subjectarea.asjc.2700.2723???
  • ???subjectarea.asjc.2400.2403???


Entra nei temi di ricerca di 'Efficient killing of human colon cancer stem cells by gammadelta T lymphocytes'. Insieme formano una fingerprint unica.

Cita questo