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 Vc9Vd2 T cell cytotoxicity. Vc9Vd2 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 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.

Todaro, M., Orlando, V., Cicero, G., Caccamo, N., Meraviglia, S., Stassi, G., et al. (2013). Chemotherapy Sensitizes Colon Cancer Initiating Cells to Vc9Vd2 T Cell-Mediated Cytotoxicity. PLOS ONE, 8(6).

Chemotherapy Sensitizes Colon Cancer Initiating Cells to Vc9Vd2 T Cell-Mediated Cytotoxicity

TODARO, Matilde;CICERO, Giuseppe;CACCAMO, Nadia Rosalia;MERAVIGLIA, Serena;STASSI, Giorgio;DIELI, Francesco
2013-01-01

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 Vc9Vd2 T cell cytotoxicity. Vc9Vd2 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 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.
2013
Todaro, M., Orlando, V., Cicero, G., Caccamo, N., Meraviglia, S., Stassi, G., et al. (2013). Chemotherapy Sensitizes Colon Cancer Initiating Cells to Vc9Vd2 T Cell-Mediated Cytotoxicity. PLOS ONE, 8(6).
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/10447/99236
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