Department of Hematology, Japanese Red Cross Nagasaki Genbaku Hospital, Nagasaki, Japan.
Department of Viral Infections, Research Institute for Microbial Diseases, Osaka University, Osaka, Japan.
Cancer Immunol Immunother. 2023 Apr;72(4):929-944. doi: 10.1007/s00262-022-03301-6. Epub 2022 Oct 1.
Adult T cell leukemia/lymphoma (ATLL) is a CD4-positive peripheral T cell lymphoma caused by human T cell lymphotropic virus type 1 (HTLV-1). Although ATLL is quite difficult to be cured, up-regulation of cellular immunity such as HTLV-1 Tax-specific cytotoxic T lymphocytes (CTLs) has been proved to be important to obtain long-term survival. At present, no efficacious method to activate ATLL-specific cellular immunity is available. This study aimed to investigate whether live attenuated varicella-zoster virus (VZV) vaccination to ATLL can activate HTLV-1 Tax-specific cellular immune response. A total of 3 indolent- and 3 aggressive-type ATLL patients were enrolled. All aggressive-type patients had the VZV vaccination after completing anti-ATLL treatment including mogamulizumab, which is a monoclonal antibody for C-C chemokine receptor 4 antigen, plus combination chemotherapy, whereas all indolent-type patients had the VZV vaccination without any antitumor treatment. Cellular immune responses including Tax-specific CTLs were analyzed at several time points of pre- and post-VZV vaccination. After the VZV vaccination, a moderate increase in 1 of 3 indolent-type patients and obvious increase in all 3 aggressive-type patients in Tax-specific CTLs percentage were observed. The increase in the cell-mediated immunity against VZV was observed in all indolent- and aggressive-type patients after VZV vaccination. To conclude, VZV vaccination to aggressive-type ATLL patients after mogamulizumab plus chemotherapy led to the up-regulation of HTLV-1 Tax-specific CTLs without any adverse event. Suppression of regulatory T lymphocytes by mogamulizumab may have contributed to increase tumor immunity in aggressive-type ATLL patients. Japan Registry of Clinical Trials number, jRCTs051180107.
成人 T 细胞白血病/淋巴瘤（ATLL）是一种由人类 T 细胞白血病病毒 1（HTLV-1）引起的 CD4 阳性外周 T 细胞淋巴瘤。虽然 ATLL 很难治愈，但细胞免疫的上调，如 HTLV-1 Tax 特异性细胞毒性 T 淋巴细胞（CTL），已被证明对获得长期生存很重要。目前，尚无有效的方法来激活 ATLL 特异性细胞免疫。本研究旨在探讨活减毒水痘带状疱疹病毒（VZV）疫苗接种对 ATLL 是否能激活 HTLV-1 Tax 特异性细胞免疫反应。共纳入 3 例惰性和 3 例侵袭性 ATLL 患者。所有侵袭性 ATLL 患者在完成包括 mogamulizumab（一种针对 C-C 趋化因子受体 4 抗原的单克隆抗体）在内的抗 ATLL 治疗后，即联合化疗后，进行了 VZV 疫苗接种，而所有惰性 ATLL 患者在未进行任何抗肿瘤治疗的情况下进行了 VZV 疫苗接种。在 VZV 疫苗接种前后的几个时间点分析了细胞免疫反应，包括 Tax 特异性 CTL。在 3 例惰性患者中的 1 例和所有 3 例侵袭性患者中观察到 Tax 特异性 CTL 百分比适度增加。在 VZV 疫苗接种后，所有惰性和侵袭性患者均观察到针对 VZV 的细胞介导免疫增加。总之，在 mogamulizumab 加化疗后，对侵袭性 ATLL 患者进行 VZV 疫苗接种可导致 HTLV-1 Tax 特异性 CTL 的上调，而无任何不良反应。mogamulizumab 对调节性 T 淋巴细胞的抑制可能有助于增加侵袭性 ATLL 患者的肿瘤免疫力。日本临床试验注册编号，jRCTs051180107。
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