Kagdi Huseini H, Demontis Maria A, Fields Paul A, Ramos Juan Carlos, Bangham Charles R M, Taylor Graham P
Section of Virology, Department of Medicine, Imperial College London, London, UK.
Department of Hematology, Guys Hospital, London, UK.
Cancer Med. 2017 Jan;6(1):298-309. doi: 10.1002/cam4.928. Epub 2016 Dec 30.
Adult T-cell leukemia/lymphoma (ATL), a human T-lymphotropic virus type 1 (HTLV-1)-associated disease, has a highly variable clinical course and four subtypes with therapeutic and prognostic implications. However, there are overlapping features between ATL subtypes and between ATL and nonmalignant (non-ATL) HTLV-1 infection complicating diagnosis and prognostication. To further refine the diagnosis and prognosis of ATL, we characterized the immunophenotype of HTLV-1-infected cells in ATL and non-ATL. A retrospective study of peripheral blood samples from 10 HTLV-1-uninfected subjects (UI), 54 HTLV-1-infected patients with non-ATL, and 22 with ATL was performed using flow cytometry. All patients with ATL had CD4 CCR4 CD26 immunophenotype and the frequency of CD4 CCR4 CD26 T cells correlated highly significantly with the proviral load in non-ATL suggesting CD4 CCR4 CD26 as a marker of HTLV-1-infected cells. Further immunophenotyping of CD4 CCR4 CD26 cells revealed that 95% patients with ATL had a CD7 (≤30% CD7 cells), whereas 95% HTLV+ non-ATL had CD7 (>30% CD7 cells) immunophenotype. All patients with aggressive ATL had a CCR7 (≥30%), whereas 92% with indolent ATL and 100% non-ATL had a CCR7 (<30%) immunophenotype. Patients with nonprogressing indolent ATL were CD127 but those with progressive lymphocytosis requiring systemic therapy had a CD127 (≤30%) immunophenotype. In summary, HTLV-1-infected cells have a CD4 CCR4 CD26 immunophenotype. Within this population, CD7 phenotype suggests a diagnosis of ATL, CCR7 phenotype identifies aggressive ATL, while CCR7 CD127 phenotype identifies progressive indolent ATL.
成人T细胞白血病/淋巴瘤（ATL）是一种与1型人类嗜T淋巴细胞病毒（HTLV-1）相关的疾病，其临床病程高度可变，有四种亚型，具有治疗和预后意义。然而，ATL亚型之间以及ATL与非恶性（非ATL）HTLV-1感染之间存在重叠特征，这使得诊断和预后判断变得复杂。为了进一步优化ATL的诊断和预后，我们对ATL和非ATL中HTLV-1感染细胞的免疫表型进行了特征分析。使用流式细胞术对10名未感染HTLV-1的受试者（UI）、54名感染HTLV-1的非ATL患者和22名ATL患者的外周血样本进行了回顾性研究。所有ATL患者均具有CD4⁺CCR4⁺CD26免疫表型，且非ATL中CD4⁺CCR4⁺CD26 T细胞的频率与前病毒载量高度显著相关，提示CD4⁺CCR4⁺CD26作为HTLV-1感染细胞的标志物。对CD4⁺CCR4⁺CD26细胞的进一步免疫表型分析显示，95%的ATL患者具有CD7⁻（CD7细胞≤30%），而95%的HTLV⁺非ATL患者具有CD7⁺（CD7细胞>30%）免疫表型。所有侵袭性ATL患者均具有CCR7⁺（≥30%），而92%的惰性ATL患者和100%的非ATL患者具有CCR7⁻（<30%）免疫表型。病情无进展的惰性ATL患者为CD127⁺，但需要全身治疗的进行性淋巴细胞增多患者具有CD127⁻（≤30%）免疫表型。总之，HTLV-1感染细胞具有CD4⁺CCR4⁺CD26免疫表型。在这一群体中，CD7表型提示ATL诊断，CCR7表型识别侵袭性ATL，而CCR7⁻CD127⁺表型识别进行性惰性ATL。
