Expansion of quiescent lung adenocarcinoma CD8+ T cells by MUC1-8-mer peptide-T2 cell-β2 microglobulin complexes.
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.
Department of Research in Biochemistry, National Institute of Respiratory Diseases 'Ismael Cosio Villegas', Mexico, DF 14080, Mexico.
J A
JA
Atzin-Méndez
Lung Cancer Laboratory, National Institute of Respiratory Diseases 'Ismael Cosio Villegas', Mexico, DF 14080, Mexico.
J S
JS
López-González
Clinical Oncology and Pneumology, National Institute of Respiratory Diseases 'Ismael Cosio Villegas', Mexico, DF 14080, Mexico.
R
R
Báez
Department of Biochemistry, Faculty of Medicine, National Autonomous University of Mexico, Mexico, DF 04510, Mexico.
M C
MC
Arenas-Del Angel
Immunobiology Laboratory, Department of Cell and Tissue Biology, Faculty of Medicine, National Autonomous University of Mexico, Mexico, DF 04510, Mexico.
L F
LF
Montaño
Experimental Laboratory for Neurodegenerative Diseases, National Institute of Neurology and Neurosurgery, Mexico, DF 14269, Mexico.
D
D
Silva-Adaya
Department of Research in Biochemistry, National Institute of Respiratory Diseases 'Ismael Cosio Villegas', Mexico, DF 14080, Mexico.
R
R
Lascurain
Department of Research in Biochemistry, National Institute of Respiratory Diseases 'Ismael Cosio Villegas', Mexico, DF 14080, Mexico.
P
P
Gorocica
D000328:Adult; D000368:Aged; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology* / Q000276:immunology; D002289:Carcinoma, Non-Small-Cell Lung / Q000276:immunology* / Q000473:pathology; D002460:Cell Line; D049109:Cell Proliferation; D018984:Epitopes, T-Lymphocyte / Q000378:metabolism*; D005260:Female; D015789:HLA-A2 Antigen / Q000378:metabolism; D006801:Humans; D008175:Lung Neoplasms / Q000276:immunology* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D018396:Mucin-1 / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology* / Q000378:metabolism; D014407:Tumor Cells, Cultured
D018984:Epitopes, T-Lymphocyte; D015789:HLA-A2 Antigen; C060192:MUC1 protein, human; D018396:Mucin-1