Development and dynamics of robust T-cell responses to CML under imatinib treatment.
Novel molecular targeted therapies, such as imatinib for chronic myelogenous leukemia (CML), represent the first agents that inhibit cancer cells more than other dividing cells, such as immune cells. We hypothesize that imatinib may create a window in which the immune response is partially restored while apoptotic leukemic cells are present, thus rendering leukemic cells immunogenic as patients enter remission. To detect and quantify antileukemia immune responses in an antigen-unbiased way, we used cryopreserved autologous pretreatment blood samples (representing predominantly leukemic cells) as stimulators to detect antileukemia T-cell responses in CML patients in remission on imatinib. We studied patients over time to address the dynamics of such responses. Our data show that antileukemia T-cell responses develop in the majority of CML patients (9 of 14) in remission and that CD4(+) T cells producing tumor necrosis factor-alpha (median 17.6%) represent the major response over interferon-gamma. This confirms the immune system's ability to respond to leukemia under certain conditions. Such responses may be further amplified as a potential therapy that synergizes with imatinib for improved control of CML.
Chen
Christiane I-U
CI
Department of Medicine, Division of Hematology, Stanford University School of Medicine, Stanford, CA 94305, USA.
Maecker
Holden T
HT
Lee
Peter P
PP
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001549:Benzamides; D002999:Clone Cells; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D000068877:Imatinib Mesylate; D007371:Interferon-gamma / Q000187:drug effects / Q000378:metabolism; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy* / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D010879:Piperazines / Q000627:therapeutic use*; D011743:Pyrimidines / Q000627:therapeutic use*; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000187:drug effects / Q000378:metabolism
D000970:Antineoplastic Agents; D001549:Benzamides; D010879:Piperazines; D011743:Pyrimidines; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma; D000068877:Imatinib Mesylate