Human T-cell leukemia virus type 1-infected cells (HTLV-1-infected cells)

Human T-cell leukemia virus type 1 (HTLV-1)-infected cells are the primary drivers of Adult T-cell leukemia/lymphoma (ATL) and HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). These cells, predominantly CD4+ T lymphocytes, are characterized by the integration of the HTLV-1 provirus into the host genome, leading to the expression of viral oncoproteins such as Tax and HBZ (Matsuoka & Jeang, 2007, Nat Rev Cancer). Tax is crucial for the early stages of transformation by activating NF-κB and other proliferative pathways, while HBZ is essential for maintaining the transformed phenotype and promoting immune evasion (Satou et al., 2006, Proc Natl Acad Sci U S A). In patients with ATL, these cells undergo clonal expansion and often express high levels of surface markers like CD25 and CCR4, which are exploited as therapeutic targets (Ishida et al., 2012, J Clin Oncol). Current treatments aim to eliminate these infected clones using targeted monoclonal antibodies, such as mogamulizumab, or by inducing apoptosis through combinations of zidovudine, interferon-alpha, and arsenic trioxide (Bazarbachi et al., 2010, J Clin Oncol). Despite these interventions, the persistence of the virus in long-lived T-cell clones and the high risk of relapse remain significant challenges in clinical management (Bangham et al., 2015, Lancet Infect Dis).

Other names

HTLV-1-transformed cellsATL cellsHTLV-I-infected T-cellsHTLV-1-positive T-cells

Therapeutic strategies targeting HTLV-1-infected cells involve multiple approaches: monoclonal antibodies such as mogamulizumab target the CCR4 receptor to induce antibody-dependent cellular cytotoxicity (ADCC) (Ishida et al., 2012, J Clin Oncol); brentuximab vedotin targets CD30 to deliver a cytotoxic payload (Ramos et al., 2017, Blood); the combination of zidovudine and interferon-alpha inhibits reverse transcription and induces p53-dependent apoptosis (Bazarbachi et al., 2010, J Clin Oncol); and arsenic trioxide promotes the degradation of the viral oncoprotein Tax (El-Sabban et al., 2000, Blood).