Back to Search
Start Over
Chemotherapy sensitizes colon cancer initiating cells to Vγ9Vδ2 T cell-mediated cytotoxicity.
- Source :
-
PloS one [PLoS One] 2013 Jun 06; Vol. 8 (6), pp. e65145. Date of Electronic Publication: 2013 Jun 06 (Print Publication: 2013). - Publication Year :
- 2013
-
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.
- Subjects :
- Adenocarcinoma genetics
Adenocarcinoma immunology
Adenocarcinoma pathology
Cell Line
Coculture Techniques
Colonic Neoplasms genetics
Colonic Neoplasms immunology
Colonic Neoplasms pathology
Cytotoxicity, Immunologic
Doxorubicin pharmacology
Fluorouracil pharmacology
Gene Expression
Humans
NK Cell Lectin-Like Receptor Subfamily K genetics
NK Cell Lectin-Like Receptor Subfamily K immunology
Neoplastic Stem Cells immunology
Neoplastic Stem Cells pathology
Primary Cell Culture
Receptors, Antigen, T-Cell, gamma-delta genetics
Receptors, TNF-Related Apoptosis-Inducing Ligand genetics
Receptors, TNF-Related Apoptosis-Inducing Ligand immunology
T-Lymphocytes, Cytotoxic cytology
TNF-Related Apoptosis-Inducing Ligand genetics
TNF-Related Apoptosis-Inducing Ligand immunology
Adenocarcinoma drug therapy
Antineoplastic Agents pharmacology
Colonic Neoplasms drug therapy
Neoplastic Stem Cells drug effects
Receptors, Antigen, T-Cell, gamma-delta immunology
T-Lymphocytes, Cytotoxic immunology
Subjects
Details
- Language :
- English
- ISSN :
- 1932-6203
- Volume :
- 8
- Issue :
- 6
- Database :
- MEDLINE
- Journal :
- PloS one
- Publication Type :
- Academic Journal
- Accession number :
- 23762301
- Full Text :
- https://doi.org/10.1371/journal.pone.0065145