人类 T 细胞白血病病毒 1 型 (HTLV-1) 在人类中建立慢性感染，并诱发称为成人 T 细胞白血病淋巴瘤 (ATL) 的 T 细胞恶性肿瘤和多种炎症性疾病，例如 HTLV-1 相关的脊髓病/热带病痉挛性截瘫（HAM/TSP）。持续性HTLV-1感染是在宿主免疫压力下建立的，因此针对HTLV-1的免疫反应被认为反映了其引起的疾病的状态。事实上，众所周知，与 HAM/TSP 患者相比，ATL 患者针对病毒抗原的细胞免疫受到抑制。在这项研究中，我们表明，分析对几种 HTLV-1 抗原（例如 Gag、Env 和 Tax）的体液免疫并测量前病毒载量是对疾病状态进行分类和预测疾病发展的有用工具。通过靶向测序，我们发现该分析方法预测的几位具有发生 ATL 高风险的携带者确实携带 ATL 驱动突变。这些携带者中HTLV-1感染细胞的克隆性仍然是多克隆的；它与白血病发生的早期阶段一致。此外，这项研究揭示了抗Gag蛋白对预测HTLV-1携带者高危人群的重要性。与这一发现一致的是，接受造血干细胞移植并达到缓解状态的患者中抗Gag细胞毒性T淋巴细胞（CTL）增加，表明抗Gag CTL对疾病控制的重要性。我们的研究结果表明，我们结合抗 HTLV-1 抗体和前病毒载量的策略可能有助于预测 HTLV-1 相关疾病的发展。© 2023 作者。约翰·威利出版的《癌症科学》

Human T-cell leukemia virus type 1 (HTLV-1) establishes chronic infection in humans and induces a T-cell malignancy called adult T-cell leukemia-lymphoma (ATL) and several inflammatory diseases such as HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). Persistent HTLV-1 infection is established under the pressure of host immunity, and therefore the immune response against HTLV-1 is thought to reflect the status of the disease it causes. Indeed, it is known that cellular immunity against viral antigens is suppressed in ATL patients compared to HAM/TSP patients. In this study, we show that profiling the humoral immunity to several HTLV-1 antigens, such as Gag, Env, and Tax, and measuring proviral load are useful tools for classifying disease status and predicting disease development. Using targeted sequencing, we found that several carriers whom this profiling method predicted to be at high risk for developing ATL indeed harbored driver mutations of ATL. The clonality of HTLV-1-infected cells in those carriers was still polyclonal; it is consistent with an early stage of leukemogenesis. Furthermore, this study revealed significance of anti-Gag proteins to predict high risk group in HTLV-1 carriers. Consistent with this finding, anti-Gag cytotoxic T lymphocytes (CTLs) were increased in patients who received hematopoietic stem cell transplantation and achieved remission state, indicating the significance of anti-Gag CTLs for disease control. Our findings suggest that our strategy that combines anti-HTLV-1 antibodies and proviral load may be useful for prediction of the development of HTLV-1-associated diseases.© 2023 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.