Chemotherapy sensitizes colon cancer initiating cells to Vγ9Vδ2 T cell-mediated cytotoxicity.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 23762301.
- Also identified by DOI 10.1371/journal.pone.0065145 and PMC identifier 3675136.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
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 Vγ9Vδ2 T cell cytotoxicity. Vγ9Vδ2 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 Vγ9Vδ2 T cells or adoptive administration of ex-vivo expanded Vγ9Vδ2 T cells at suitable intervals after chemotherapy may substantially increase anti-tumor activities and represent a novel strategy for colon cancer immunotherapy.
Medical subject headings
- Adenocarcinoma
- Antineoplastic Agents
- Colonic Neoplasms
- Neoplastic Stem Cells
- Receptors, Antigen, T-Cell, gamma-delta
- T-Lymphocytes, Cytotoxic