title: Autoimmune B-cell lymphopenia after successful adoptive therapy with telomerase-specific T lymphocytes.
abstract: Telomerase reverse transcriptase (TERT) is a good candidate for cancer immunotherapy because it is overexpressed in 85% of all human tumors and implicated in maintenance of the transformed phenotype. TERT-based cancer vaccines have been shown to be safe, not inducing any immune-related pathology, but their impact on tumor progression is modest. Here we show that adoptive cell therapy with the use of high-avidity T lymphocytes reactive against telomerase can control the growth of different established tumors. Moreover, in transgenic adenocarcinoma mouse prostate mice, which develop prostate cancer, TERT-based adoptive cell therapy halted the progression to more aggressive and poorly differentiated tumors, significantly prolonging mouse survival. We also demonstrated that human tumors, including Burkitt lymphoma, and human cancer stem cells, are targeted in vivo by TERT-specific cytotoxic T lymphocytes. Effective therapy with T cells against telomerase, different from active vaccination, however, led to autoimmunity marked by a consistent, although transient, B-cell depletion in primary and secondary lymphoid organs, associated with alteration of the spleen cytoarchitecture. These results indicate B cells as an in vivo target of TERT-specific cytotoxic T lymphocytes during successful immunotherapy.
authors.affiliation: Department of Oncology and Surgical Sciences, Padova, Italy.
authors.forename: Stefano
authors.initials: S
authors.lastname: Ugel
authors.forename: Elisa
authors.initials: E
authors.lastname: Scarselli
authors.forename: Manuela
authors.initials: M
authors.lastname: Iezzi
authors.forename: Carmela
authors.initials: C
authors.lastname: Mennuni
authors.forename: Tania
authors.initials: T
authors.lastname: Pannellini
authors.forename: Francesco
authors.initials: F
authors.lastname: Calvaruso
authors.forename: Barbara
authors.initials: B
authors.lastname: Cipriani
authors.forename: Raffaele
authors.initials: R
authors.lastname: De Palma
authors.forename: Lucia
authors.initials: L
authors.lastname: Ricci-Vitiani
authors.forename: Elisa
authors.initials: E
authors.lastname: Peranzoni
authors.forename: Piero
authors.initials: P
authors.lastname: Musiani
authors.forename: Paola
authors.initials: P
authors.lastname: Zanovello
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Bronte
mesh_terms: D000230:Adenocarcinoma / Q000276:immunology / Q000628:therapy*; D019264:Adoptive Transfer / Q000379:methods*; D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology / Q000473:pathology; D001854:Bone Marrow Cells / Q000473:pathology; D019496:Cancer Vaccines; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms; D004195:Disease Models, Animal; D015789:HLA-A2 Antigen / Q000235:genetics / Q000276:immunology; D008175:Lung Neoplasms; D008231:Lymphopenia / Q000473:pathology*; D008297:Male; D008545:Melanoma; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009368:Neoplasm Transplantation; D011471:Prostatic Neoplasms / Q000276:immunology / Q000628:therapy*; D012878:Skin Neoplasms; D013154:Spleen / Q000473:pathology; D013601:T-Lymphocytes / Q000276:immunology / Q000637:transplantation*; D019098:Telomerase / Q000276:immunology*
chemical_list: D019496:Cancer Vaccines; D015789:HLA-A2 Antigen; C509186:TERT protein, human; D019098:Telomerase; C509187:Tert protein, mouse