Journal
PLOS ONE
Volume 8, Issue 6, Pages -Publisher
PUBLIC LIBRARY SCIENCE
DOI: 10.1371/journal.pone.0065145
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Funding
- Italian Ministry for Instruction, University and Research [2008L57JXW]
- Italian Ministry of Health
- Istituto Superiore di Sanita Oncoproteomic Project [2007-527/B/3A/3]
- University of Palermo
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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 of immune-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 V gamma 9V delta 2 T cell cytotoxicity. V gamma 9V delta 2 T cell cytotoxicity was largely mediated by TRAIL interaction with DR5, following NKG2D-dependent recognition of colon CIC targets. We conclude that in vivo activation of V gamma 9V delta 2 T cells or adoptive administration of ex-vivo expanded V gamma 9V delta 2 T cells at suitable intervals after chemotherapy may substantially increase anti-tumor activities and represent a novel strategy for colon cancer immunotherapy.
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