Understanding the Immunopathology of HTLV-1-Associated Adult T-Cell Leukemia/Lymphoma: A Comprehensive Review

Abstract

Human T-cell leukemia virus type-1 (HTLV-1) causes adult T-cell leukemia/lymphoma (ATL). HTLV-1 carriers have a lifelong asymptomatic balance between infected cells and host antiviral immunity; however, 5–10% of carriers lose this balance and develop ATL. Coinfection with Strongyloides promotes ATL development, suggesting that the immunological status of infected individuals is a determinant of HTLV-1 pathogenicity. As CD4+ T cells play a central role in host immunity, the deregulation of their function and differentiation via HTLV-1 promotes the immune evasion of infected T cells. During ATL development, the accumulation of genetic and epigenetic alterations in key host immunity-related genes further disturbs the immunological balance. Various approaches are available for treating these abnormalities; however, hematopoietic stem cell transplantation is currently the only treatment with the potential to cure ATL. The patient’s immune state may contribute to the treatment outcome. Additionally, the activity of the anti-CC chemokine receptor 4 antibody, mogamulizumab, depends on immune function, including antibody-dependent cytotoxicity. In this comprehensive review, we summarize the immunopathogenesis of HTLV-1 infection in ATL and discuss the clinical findings that should be considered when developing treatment strategies for ATL.

Заболевания, Ассоциированные С Т-Лимфотропным Вирусом Типа 1 Человека (HTLV-1)

“…При заражении HTLV-1 наблюдается нарушение их функции и дифференцировки, что приводит к иммунному уклонению инфицированных Т-клеток. Нарушение иммунного баланса при АТLL усугубляется накоплением генетических и эпигенетических изменений в ключевых генах, связанных с иммунитетом хозяина [6]. В механизмах канцерогенеза решающую роль играет ангиогенез, то есть формирование новых кровеносных сосудов.…”

HTLV-1: Neglected Virus in Southeast Asia for Decades

“…However, unlike other oncogenic viruses, this virus has the characteristic of transmission through breastfeeding. Given the crucial role of breastfeeding in both nutritional and emotional aspects between mother and infant, it becomes an important source of infection (Nakahata et al, 2023).…”

EZH2-Myc Hallmark in Oncovirus/Cytomegalovirus Infections and Cytomegalovirus’ Resemblance to Oncoviruses

“…Single-cell analyses have revealed a concurrent reduction in B cells and an elevation in myeloid cells in ATL. These myeloid cells also exhibit elevated expression of activation markers like CD64 and immune checkpoint molecules, for instance, PD-1 [ 114 ]. Moreover, MCC cell lines show a reduction in HLA class I expression [ 115 ].…”