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Expansion of quiescent lung adenocarcinoma CD8+ T cells by MUC1-8-mer peptide-T2 cell-ß2 microglobulin complexes.
Atzin-Méndez, J A; López-González, J S; Báez, R; Arenas-Del Angel, M C; Montaño, L F; Silva-Adaya, D; Lascurain, R; Gorocica, P.
Afiliação
  • Atzin-Méndez JA; Department of Research in Biochemistry, National Institute of Respiratory Diseases 'Ismael Cosio Villegas', Mexico, DF 14080, Mexico.
  • López-González JS; Lung Cancer Laboratory, National Institute of Respiratory Diseases 'Ismael Cosio Villegas', Mexico, DF 14080, Mexico.
  • Báez R; Clinical Oncology and Pneumology, National Institute of Respiratory Diseases 'Ismael Cosio Villegas', Mexico, DF 14080, Mexico.
  • Arenas-Del Angel MC; Department of Biochemistry, Faculty of Medicine, National Autonomous University of Mexico, Mexico, DF 04510, Mexico.
  • Montaño LF; Immunobiology Laboratory, Department of Cell and Tissue Biology, Faculty of Medicine, National Autonomous University of Mexico, Mexico, DF 04510, Mexico.
  • Silva-Adaya D; Experimental Laboratory for Neurodegenerative Diseases, National Institute of Neurology and Neurosurgery, Mexico, DF 14269, Mexico.
  • Lascurain R; Department of Research in Biochemistry, National Institute of Respiratory Diseases 'Ismael Cosio Villegas', Mexico, DF 14080, Mexico.
  • Gorocica P; Department of Research in Biochemistry, National Institute of Respiratory Diseases 'Ismael Cosio Villegas', Mexico, DF 14080, Mexico.
Oncol Rep ; 35(1): 33-42, 2016 Jan.
Article em En | MEDLINE | ID: mdl-26498650
Adoptive immunotherapy requires the isolation of CD8+ T cells specific for tumor-associated antigens, their expansion in vitro and their transfusion to the patient to mediate a therapeutic effect. MUC1 is an important adenocarcinoma antigen immunogenic for T cells. The MUC1-derived SAPDTRPA (MUC1-8-mer) peptide is a potent epitope recognized by CD8+ T cells in murine models. Likewise, the T2 cell line has been used as an antigen-presenting cell to activate CD8+ T cells, but so far MUC1 has not been assessed in this context. We evaluated whether the MUC1-8-mer peptide can be presented by T2 cells to expand CD25+CD8+ T cells isolated from HLA-A2+ lung adenocarcinoma patients with stage III or IV tumors. The results showed that MUC1-8-mer peptide-loaded T2 cells activated CD8+ T cells from cancer HLA-A2+ patients when anti-CD2, anti-CD28 antibodies and IL-2 were added. The percentage of CD25+CD8+ T cells was 3-fold higher than those in the non-stimulated cells (P=0.018). HLA-A2+ patient cells showed a significant difference (2.3-fold higher) in activation status than HLA-A2+ healthy control cells (P=0.04). Moreover, 77.6% of MUC1-8-mer peptide-specific CD8+ T cells proliferated following a second stimulation with MUC1-8-mer peptide-loaded T2 cells after 10 days of cell culture. There were significant differences in the percentage of basal CD25+CD8+ T cells in relation to the cancer stage; this difference disappeared after MUC1-8-mer peptide stimulation. In conclusion, expansion of CD25+CD8+ T cells by MUC1-8 peptide-loaded T2 cells plus costimulatory signals via CD2, CD28 and IL-2 can be useful in adoptive immunotherapy.
Assuntos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Linfócitos T Citotóxicos / Carcinoma Pulmonar de Células não Pequenas / Linfócitos T CD8-Positivos / Mucina-1 / Epitopos de Linfócito T / Neoplasias Pulmonares Limite: Adult / Aged / Female / Humans / Male / Middle aged Idioma: En Revista: Oncol Rep Assunto da revista: NEOPLASIAS Ano de publicação: 2016 Tipo de documento: Article País de afiliação: México País de publicação: Grécia

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Linfócitos T Citotóxicos / Carcinoma Pulmonar de Células não Pequenas / Linfócitos T CD8-Positivos / Mucina-1 / Epitopos de Linfócito T / Neoplasias Pulmonares Limite: Adult / Aged / Female / Humans / Male / Middle aged Idioma: En Revista: Oncol Rep Assunto da revista: NEOPLASIAS Ano de publicação: 2016 Tipo de documento: Article País de afiliação: México País de publicação: Grécia