Abstract

Colon cancer comprises a small population of cancer initiating stem cells (CIC) that is responsible for tumor maintenance and resistance to anti-cancer therapies, possibly allowing for tumor recapitulation once treatment stops. Combinations ofimmune-based therapies with chemotherapy and other anti-tumor agents may be of significant clinical benefit in the treatment of colon cancer. However, cellular immune-based therapies have not been experimented yet in the population of colon CICs. Here, we demonstrate that treatment with low concentrations of commonly used chemotherapeutic agents, 5-fluorouracyl and doxorubicin, sensitize colon CICs to Vc9Vd2 T cell cytotoxicity. Vc9Vd2 T cell cytotoxicity was largelymediated by TRAIL interaction with DR5, following NKG2D-dependent recognition of colon CIC targets. We conclude that in vivo activation of Vc9Vd2 T cells or adoptive administration of ex-vivo expanded Vc9Vd2 T cells at suitable intervals after chemotherapy may substantially increase anti-tumor activities and represent a novel strategy for colon cancer immunotherapy.
Lingua originaleEnglish
Numero di pagine0
RivistaPLoS One
Volume8
Stato di pubblicazionePublished - 2013

All Science Journal Classification (ASJC) codes

  • ???subjectarea.asjc.1300.1300???
  • ???subjectarea.asjc.1100.1100???
  • General

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