title: Antigen-specific cytotoxic T lymphocytes can target chemoresistant side-population tumor cells in Hodgkin lymphoma.
abstract: Side-population (SP) analysis has been used to identify progenitor cells from normal and malignant tissues as well as revealing tumor cells with increased resistance to radiation and chemotherapy. Despite enhanced chemoresistance, tumor SP cells may still express tumor-associated antigens (TAAs), which may render them susceptible to elimination by the immune system. In this study, we show that both Hodgkin lymphoma (HL) cell lines and primary HL tumor samples contain a distinct SP phenotype. Importantly, while these cells showed increased resistance to gemcitabine, a commonly used drug for the treatment of refractory HL, HL SP cells also expressed higher levels of the TAAs MAGEA4, SSX2, survivin, and NY-ESO-1, which allowed them to be specifically recognized and killed by TAA-specific cytotoxic T lymphocytes. This study suggests that chemoresistant HL SP cells can be targeted by the immune system, providing a rationale for combined chemotherapy and immunotherapy for the treatment of HL.
authors.affiliation: Center for Cell and Gene Therapy, Department of Pediatrics, Baylor College of Medicine, The Methodist Hospital and Texas Children's Cancer Center, Houston, TX 77030, USA. jashafer@txccc.org
authors.forename: Jessica A
authors.initials: JA
authors.lastname: Shafer
authors.forename: Conrad R
authors.initials: CR
authors.lastname: Cruz
authors.forename: Ann M
authors.initials: AM
authors.lastname: Leen
authors.forename: Stephanie
authors.initials: S
authors.lastname: Ku
authors.forename: An
authors.initials: A
authors.lastname: Lu
authors.forename: Alexandra
authors.initials: A
authors.lastname: Rousseau
authors.forename: Helen E
authors.initials: HE
authors.lastname: Heslop
authors.forename: Cliona M
authors.initials: CM
authors.lastname: Rooney
authors.forename: Catherine M
authors.initials: CM
authors.lastname: Bollard
authors.forename: Aaron E
authors.initials: AE
authors.lastname: Foster
mesh_terms: D000951:Antigens, Neoplasm / Q000276:immunology; D000964:Antimetabolites, Antineoplastic / Q000627:therapeutic use; D003841:Deoxycytidine / Q000031:analogs & derivatives / Q000627:therapeutic use; D019008:Drug Resistance, Neoplasm; D005434:Flow Cytometry; D006689:Hodgkin Disease / Q000145:classification / Q000276:immunology* / Q000628:therapy*; D006801:Humans; D007124:Immunoenzyme Techniques; D007167:Immunotherapy; D011379:Prognosis; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014407:Tumor Cells, Cultured; D000093542:Gemcitabine
chemical_list: D000951:Antigens, Neoplasm; D000964:Antimetabolites, Antineoplastic; D003841:Deoxycytidine; D000093542:Gemcitabine