Chemotherapy sensitizes colon cancer initiating cells to Vγ9Vδ2 T cell-mediated cytotoxicity.

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-...

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Autores principales:	Matilde Todaro, Valentina Orlando, Giuseppe Cicero, Nadia Caccamo, Serena Meraviglia, Giorgio Stassi, Francesco Dieli
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2013
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/6aa19933711648bb8230a8a26df4a6b0
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spelling	oai:doaj.org-article:6aa19933711648bb8230a8a26df4a6b02021-11-18T07:42:48ZChemotherapy sensitizes colon cancer initiating cells to Vγ9Vδ2 T cell-mediated cytotoxicity.1932-620310.1371/journal.pone.0065145https://doaj.org/article/6aa19933711648bb8230a8a26df4a6b02013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23762301/?tool=EBIhttps://doaj.org/toc/1932-6203Colon 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.Matilde TodaroValentina OrlandoGiuseppe CiceroNadia CaccamoSerena MeravigliaGiorgio StassiFrancesco DieliPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 6, p e65145 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Matilde Todaro Valentina Orlando Giuseppe Cicero Nadia Caccamo Serena Meraviglia Giorgio Stassi Francesco Dieli Chemotherapy sensitizes colon cancer initiating cells to Vγ9Vδ2 T cell-mediated cytotoxicity.
description	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.
format	article
author	Matilde Todaro Valentina Orlando Giuseppe Cicero Nadia Caccamo Serena Meraviglia Giorgio Stassi Francesco Dieli
author_facet	Matilde Todaro Valentina Orlando Giuseppe Cicero Nadia Caccamo Serena Meraviglia Giorgio Stassi Francesco Dieli
author_sort	Matilde Todaro
title	Chemotherapy sensitizes colon cancer initiating cells to Vγ9Vδ2 T cell-mediated cytotoxicity.
title_short	Chemotherapy sensitizes colon cancer initiating cells to Vγ9Vδ2 T cell-mediated cytotoxicity.
title_full	Chemotherapy sensitizes colon cancer initiating cells to Vγ9Vδ2 T cell-mediated cytotoxicity.
title_fullStr	Chemotherapy sensitizes colon cancer initiating cells to Vγ9Vδ2 T cell-mediated cytotoxicity.
title_full_unstemmed	Chemotherapy sensitizes colon cancer initiating cells to Vγ9Vδ2 T cell-mediated cytotoxicity.
title_sort	chemotherapy sensitizes colon cancer initiating cells to vγ9vδ2 t cell-mediated cytotoxicity.
publisher	Public Library of Science (PLoS)
publishDate	2013
url	https://doaj.org/article/6aa19933711648bb8230a8a26df4a6b0
work_keys_str_mv	AT matildetodaro chemotherapysensitizescoloncancerinitiatingcellstovg9vd2tcellmediatedcytotoxicity AT valentinaorlando chemotherapysensitizescoloncancerinitiatingcellstovg9vd2tcellmediatedcytotoxicity AT giuseppecicero chemotherapysensitizescoloncancerinitiatingcellstovg9vd2tcellmediatedcytotoxicity AT nadiacaccamo chemotherapysensitizescoloncancerinitiatingcellstovg9vd2tcellmediatedcytotoxicity AT serenameraviglia chemotherapysensitizescoloncancerinitiatingcellstovg9vd2tcellmediatedcytotoxicity AT giorgiostassi chemotherapysensitizescoloncancerinitiatingcellstovg9vd2tcellmediatedcytotoxicity AT francescodieli chemotherapysensitizescoloncancerinitiatingcellstovg9vd2tcellmediatedcytotoxicity
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Chemotherapy sensitizes colon cancer initiating cells to Vγ9Vδ2 T cell-mediated cytotoxicity.

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