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Cancer Lett ; 494: 47-57, 2020 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-32829008

RESUMO

Hsp60sp, a signal peptide derived from the leader sequence of heat shock protein 60 kDa (Hsp60), is a Qa-1/HLA-E-binding peptide. We previously showed that Hsp60sp-specific CD8+ T cells are involved in the immunoregulation of autoimmune diseases by controlling the response of self-reactive lymphocytes. Here, we report that Hsp60sp-specific CD8+ T cells killed malignant lymphocytes in vitro independently of transporter associated with antigen processing (TAP) and classical MHC-I expression. Induction of this cytotoxic T lymphocyte (CTL) response in vivo, either by adoptive transfer of in vitro-amplified CTLs or peptide-loaded dendritic cell immunization, resulted in effective control of lymphoid tumors, including TAP- or classical MHC-I-deficient cells. Hsp60sp-specific immune activation combined with programmed cell death protein 1 (PD-1) blocking synergistically restrained mouse lymphoma development. Importantly, Hsp60sp-specific CD8+ T cells did not negatively affect normal tissues and cells. Our data suggest that Hsp60sp-based immunotherapy is an inviting strategy to control lymphoid malignancies.


Assuntos
Linfócitos T CD8-Positivos/imunologia , Chaperonina 60/química , Células Dendríticas/imunologia , Inibidores de Checkpoint Imunológico/administração & dosagem , Linfoma/terapia , Proteínas Mitocondriais/química , Sinais Direcionadores de Proteínas/fisiologia , Linfócitos T Citotóxicos/imunologia , Animais , Apresentação de Antígeno , Linfócitos T CD8-Positivos/transplante , Linhagem Celular , Chaperonina 60/imunologia , Terapia Combinada , Células Dendríticas/transplante , Feminino , Antígenos de Histocompatibilidade Classe I/metabolismo , Inibidores de Checkpoint Imunológico/farmacologia , Imunização , Linfoma/imunologia , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Proteínas Mitocondriais/imunologia , Linfócitos T Citotóxicos/transplante
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