title: Intracellular cytokine analysis of interferon-gamma in T cells of patients with chronic myeloid leukemia.
abstract: The role of T cells in eradicating leukemic cells has been well demonstrated for chronic myeloid leukemia (CML). Type 1 (T1) T-cell cytokines play a major role in this antileukemic immune effect. Studies in cancer patients have demonstrated a decreased T1 cytokine production, measured by enzyme-linked immunosorbent assay (ELISA), in cultures of peripheral blood mononuclear cells. This observation of malignancy-related suppressed T1 cytokines also occurs in untreated chronic-phase (CP) CML, raising the question of the influence of different CML treatment regimens on this immunosuppression. Intracellular flow cytometry (ICF) has facilitated the evaluation of cytokines on a single-cell level. This study analyzed T1 (interferon-gamma) cytokine production in purified peripheral blood T cells by ICF, comparing different therapy approaches for CML. Twenty-one newly diagnosed CP CML patients were compared with 24 patients treated with interferon-alpha (IFN-alpha) and to 30 allogeneic bone marrow transplant (BMT) recipients (BCR-ABL negative by reverse-transcriptase polymerase chain reaction, and free of, or having only limited graft-versus-host disease at the time of study). Thirty-seven healthy controls were included. Our results showed a significantly decreased T-cell IFN-gamma synthesis in CP CML patients in relation to healthy controls (P = 0.0007). Treatment with IFN-alpha resulted in a shift from immunosuppression--documented for the group of untreated patients--to immunopotentiation, with an increase of T-cell IFN-gamma production (P = 0.0266). Notably, BMT enhanced IFN-gamma production of T cells to a level not only exceeding untreated patients (P < 0.0001) but also healthy volunteers (P < 0.0001). The observation of T1 cytokine up-regulation with IFN-alpha therapy indicates that enhanced T-cell function may be achievable in patients with CML, even in the absence of an allo-response.
authors.affiliation: Department of Medicine (Hematology/Oncology), Bone Marrow Transplantation Service, Princess Margaret Hospital, Ontario Cancer Institute, Toronto, Ontario, Canada. jaswald@uhnres.utoronto.ca
authors.forename: Jorg M
authors.initials: JM
authors.lastname: Aswald
authors.forename: Jeffrey H
authors.initials: JH
authors.lastname: Lipton
authors.forename: Hans A
authors.initials: HA
authors.lastname: Messner
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D016026:Bone Marrow Transplantation; D017252:CD3 Complex / Q000096:biosynthesis; D016207:Cytokines / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D016898:Interferon-alpha / Q000097:blood; D007371:Interferon-gamma / Q000097:blood*; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000097:blood*; D008297:Male; D008875:Middle Aged; D013601:T-Lymphocytes / Q000378:metabolism*; D015854:Up-Regulation
chemical_list: D017252:CD3 Complex; D016207:Cytokines; D016898:Interferon-alpha; D007371:Interferon-gamma