ICSBP-mediated immune protection against BCR-ABL-induced leukemia requires the CCL6 and CCL9 chemokines.
Interferon (IFN) is effective at inducing complete remissions in patients with chronic myelogenous leukemia (CML), and evidence supports an immune mechanism. Here we show that the type I IFNs (alpha and beta) regulate expression of the IFN consensus sequence-binding protein (ICSBP) in BCR-ABL-transformed cells and as shown previously for ICSBP, induce a vaccine-like immunoprotective effect in a murine model of BCR-ABL-induced leukemia. We identify the chemokines CCL6 and CCL9 as genes prominently induced by the type I IFNs and ICSBP, and demonstrate that these immunomodulators are required for the immunoprotective effect of ICSBP expression. Insights into the role of these chemokines in the antileukemic response of IFNs suggest new strategies for immunotherapy of CML.
Nardi
Valentina
V
Division of Hematology/Oncology, Children's Hospital Boston, MA 02115, USA.
Naveiras
Olaia
O
Azam
Mohammad
M
Daley
George Q
GQ
D000818:Animals; D019742:Chemokines, CC / Q000096:biosynthesis / Q000276:immunology*; D004195:Disease Models, Animal; D005260:Female; D015973:Gene Expression Regulation, Leukemic / Q000187:drug effects* / Q000276:immunology; D016313:Genes, abl / Q000276:immunology*; D006801:Humans; D050835:Interferon Regulatory Factors / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D007370:Interferon Type I / Q000276:immunology / Q000378:metabolism / Q000494:pharmacology*; D020014:K562 Cells; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy / Q000276:immunology* / Q000378:metabolism; D019402:Macrophage Inflammatory Proteins / Q000096:biosynthesis / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D000099185:Interferon Regulatory Factor-8
D019742:Chemokines, CC; D050835:Interferon Regulatory Factors; D007370:Interferon Type I; D019402:Macrophage Inflammatory Proteins; D000099185:Interferon Regulatory Factor-8; C095218:Ccl9 protein, mouse; C070959:Ccl6 protein, mouse