Chemotherapy sensitizes colon cancer initiating cells to V?9V?2 T cell-mediated cytotoxicity.

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 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?9V?2 T cell cytotoxicity. V?9V?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?9V?2 T cells or adoptive administration of ex-vivo expanded V?9V?2 T cells at suitable intervals after chemotherapy may substantially increase anti-tumor activities and represent a novel strategy for colon cancer immunotherapy.

SUBMITTER: Todaro M 

PROVIDER: S-EPMC3675136 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature