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* Institut National de la Santé et de la Recherche Médicale (INSERM) Equipe Avenir, Unité 561, Hôpital St-Vincent de Paul, Paris; INSERM Unité 445, Equipe tumeurs, Immunité, Immunothérapie; Department of Hematology, Hôpital Henri Mondor, Créteil, France; Max-Planck-Institute of Immunobiology, Freiburg, Germany; ¶ INSERM Unité 580, Hôpital Necker, Paris, France; || Research Centre, Centre Hospitalier Universitaire La Mitetric, Poitiers, France; # Laboratoire Protéomique and MicroAnalyse des Protéines, Institut Cochin de Génétique moléculaire-Hôpital Cochin, Paris, France; and** Department of Hematology, Hôpital Necker, Paris, France
Identification of tumor-associated Ags is a prerequisite for vaccine-based and adoptive immune therapies. Some tumor-associated Ags elicit specific CD8 T cells in patients with chronic myeloid leukemia (CML). Here, we characterized ex vivo responses of CD8 T cells from CML patients to extrajunction bcr-abl peptides and telomerase 540–548 hTert, PR1, and WT1 peptides. CML-specific CD8 T cells were present in most treated patients and were usually multiepitopic: WT1, hTert, PR1, and bcr74 tetramer+ cells were detected in 85, 82, 67, and 61% of patients, respectively. The breadth and magnitude of these responses did not differ significantly according to treatment or disease status. CML-specific tetramer+ CD8 T cells had a predominantly memory phenotype, an intermediate perforin content, and low intracellular IFN-
accumulation in the presence of the relevant peptide. However, in short-term culture with HLA-matched leukemia cells, the patients’ memory T cells were specifically reactivated to become IFN--producing effector cells, suggesting that CD8 T cell precursors with lytic potential are present in vivo and can be activated by appropriate stimulation. In conclusion, this study shows that multiepitopic tumor-specific CD8 T cell responses occur naturally in most CML patients, opening the way to new strategies for enhancing anti-CML immunity, in particular in patients with minimal residual disease.
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