IFN-β induces greater antiproliferative and proapoptotic effects and increased p53 signaling compared with IFN-α in PBMCs of Adult T-cell Leukemia/Lymphoma patients

Adult T-cell Leukemia/Lymphoma (ATLL) is an aggressive T-cell malignancy with a poorly understood pathology that manifests from human T-lymphotropic virus type I (HTLV-1) infected T-cells, typically after long latency periods (430 years). Current treatment regimens for ATLL include zidovudine (AZT) and interferon alpha (IFN-α) combination therapy. The established usage of IFN-α in the treatment of ATLL is largely empirical in origin. The effects of the other widely used IFN subtype, IFN-β, have not been thoroughly examined in this setting, even though IFN-β’s more potent induction of antiproliferative and apoptotic pathways has been described in solid cancers. Few studies have compared the effects of IFN-α versus those of IFN-β in ATLL and these were generally performed in cell lines, rather than primary patient cells. In vitro experiments with IFN-α using cell lines report minimal effects of IFN-α on the viability of HTLV-1-infected T-cells and viral replication, in contrast to the high in vivo response rates obtained by this therapy. Reports regarding in vitro and in vivo activity of IFN-β in this context also seem contradictory: in vitro experiments showed no antiproliferative action of IFN-β, while a single early in vivo trial using IFN-β reported promising results, with 50% of six treated patients achieving partial response to treatment using IFN-β monotherapy. The reported success rate of this IFN-β monotherapy was comparable to early AZT/IFN-α combination therapy trials where 67% of 24 treated patients achieved partial response. We performed the first direct comparison between the response to IFN-α and IFN-β in ex vivo ATLL patient PBMCs. We analyzed samples obtained between 2001 and 2007 from 9 men and 13 women aged 21–78 years (median 47.5), diagnosed as HIV negative and definite ATLL with serology, inverted PCR and/or flow cytometry, at the ‘Hospital Universitário Professor Edgar Santos’ (HUPES) in Salvador, Bahia, Brazil. Seven of these patients were classified as acute, ten as smoldering, three as chronic and two as lymphoma according to Shimoyama criteria. This study was approved by the Ethics Review Board of HUPES (number 32050106). Data handling and processing was additionally