Expansion of quiescent lung adenocarcinoma CD8+ T cells by MUC1-8-mer peptide-T2 cell-β2 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.

doi:10.3892/or.2015.4328

Expansion of quiescent lung adenocarcinoma CD8+ T cells by MUC1-8-mer peptide-T2 cell-β2 microglobulin complexes

Authors:
- J. A. Atzin-Méndez
- J. S. López-González
- R. Báez
- M. C. Arenas-Del Angel
- L. F. Montaño
- D. Silva-Adaya
- R. Lascurain
- P. Gorocica
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Affiliations: Department of Research in Biochemistry, National Institute of Respiratory Diseases ‘Ismael Cosio Villegas’, Mexico, DF 14080, Mexico, Lung Cancer Laboratory, National Institute of Respiratory Diseases ‘Ismael Cosio Villegas’, Mexico, DF 14080, Mexico, Clinical Oncology and Pneumology, National Institute of Respiratory Diseases ‘Ismael Cosio Villegas’, Mexico, DF 14080, Mexico, Department of Biochemistry, Faculty of Medicine, National Autonomous University of Mexico, Mexico, DF 04510, Mexico, Immunobiology Laboratory, Department of Cell and Tissue Biology, Faculty of Medicine, National Autonomous University of Mexico, Mexico, DF 04510, Mexico, Experimental Laboratory for Neurodegenerative Diseases, National Institute of Neurology and Neurosurgery, Mexico, DF 14269, Mexico
Published online on: October 13, 2015 https://doi.org/10.3892/or.2015.4328
Pages: 33-42
Copyright: © Atzin-Méndez et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

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.

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