Chemotherapy Sensitizes Colon Cancer Initiating Cells to Vγ9Vδ2 T Cell-Mediated Cytotoxicity

6533b834fe1ef96bd129d82d

RESEARCH PRODUCT

Chemotherapy Sensitizes Colon Cancer Initiating Cells to Vγ9Vδ2 T Cell-Mediated Cytotoxicity

Matilde Todaro Serena Meraviglia Valentina Orlando Francesco Dieli Nadia Caccamo Giuseppe Cicero Giorgio Stassi

subject

Cytotoxicity Immunologic Colorectal cancer medicine.medical_treatment Cancer Treatment Gene Expression Pharmacology TNF-Related Apoptosis-Inducing Ligand Cancer immunotherapy Basic Cancer Research Immune Response education.field_of_study Multidisciplinary T Cells Q Colon Adenocarcinoma R Receptors Antigen T-Cell gamma-delta medicine.anatomical_structure Oncology NK Cell Lectin-Like Receptor Subfamily K Colonic Neoplasms Neoplastic Stem Cells Medicine Fluorouracil Immunotherapy Research Article Tumor Immunology Immune Cells Science T cell Primary Cell Culture Immunology Population Antineoplastic Agents Adenocarcinoma Biology Cell Line Immune system Gastrointestinal Tumors medicine Humans education Biology Immune Evasion Immunity Cancers and Neoplasms Cancer Immunotherapy Immunologic Subspecialties medicine.disease Coculture Techniques Receptors TNF-Related Apoptosis-Inducing Ligand Doxorubicin Cancer research Clinical Immunology T cell mediated cytotoxicity T-Lymphocytes Cytotoxic DR5 c9Vd2

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 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.

year	journal	country	edition	language
2013-01-01	PLoS ONE

https://doi.org/10.1371/journal.pone.0065145