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从人嗜T淋巴细胞病毒1型相关细支气管肺泡疾病患者的治疗过程中揭示程序性死亡受体配体1和自然杀伤细胞活性作为预测治疗疗效生物标志物的治疗前景及应用价值

ANK Therapeutic Prospects and Usefulness of PD-L1 and NK Activity as Biomarkers for Predicting Treatment Efficacy Revealed from the Treatment Course of Patients with HTLV-1-Associated Bronchioloalveolar Disease.

作者信息

Nagai Kenjiro, Nagai Syo, Okubo Yuji, Teshigawara Keisuke

机构信息

Medical Corporation Ebino Centro Clinic, Ebino City, Miyazaki Prefecture, Japan.

Department of Medicine, Respiratory Disease Center, Yokohama City University School of Medicine, Yokohama City, Kanagawa Prefecture, Japan.

出版信息

Cancer Med J. 2023;6(1):30-36. Epub 2022 Sep 13.

Abstract

Adult T-cell leukemia/lymphoma (ATL) is a peripheral T-cell neoplasm with poor prognosis that can present as HTLV-1-associated bronchioloalveolar disease (HABA). Chemotherapy is recommended for ATL; however, it is not very effective against all types of ATL. Furthermore, there are no effective treatments for smoldering HABA-associated ATL. We present a case in which amplified natural killer cell (ANK) therapy was effective in a woman in her early 80s who was previously diagnosed with ATL-related smoldering HABA and presented with dyspnea and productive cough on exertion. The symptoms were suppressed for approximately 10 months after the first treatment, but then gradually worsened. About a year later, a second treatment was followed by mild side effects. Suppression of ATL cell proliferation by repeated doses of ANK therapy appears to be effective in this patient. The therapeutic effect was high even with long treatment intervals, and the efficacy and safety of repeated treatments have been demonstrated. ANK therapy is expected to be the mainstay of treatment ATL and HABA. ANK therapy has been reported to kill PD-L1 positive tumor cells and some solid tumors with excellent responses have many PD-L1-positive tumor cells. ANK therapy is thought to be effective for ATL because there are many PD-L1-positive tumor cells. Furthermore, administration of activated NK cells may increase tumor-killing activity in those patients with reduced NK activity. While future studies are needed, PD-L1 positive rate and NK activity may be biomarkers for the effectiveness of ANK therapy.

摘要

成人T细胞白血病/淋巴瘤(ATL)是一种预后较差的外周T细胞肿瘤,可表现为与人类T淋巴细胞病毒1型(HTLV-1)相关的细支气管肺泡疾病(HABA)。推荐对ATL进行化疗;然而,它对所有类型的ATL并非都非常有效。此外,对于隐匿性HABA相关的ATL没有有效的治疗方法。我们报告了一例80岁出头的女性病例,扩增自然杀伤细胞(ANK)疗法对其有效。该女性此前被诊断为与ATL相关的隐匿性HABA,出现劳力性呼吸困难和咳痰。首次治疗后症状缓解约10个月,但随后逐渐恶化。大约一年后进行了第二次治疗,伴有轻度副作用。重复给予ANK疗法抑制ATL细胞增殖在该患者中似乎有效。即使治疗间隔时间长,治疗效果仍很高,且已证明重复治疗的有效性和安全性。ANK疗法有望成为治疗ATL和HABA的主要方法。据报道,ANK疗法可杀死PD-L1阳性肿瘤细胞,一些对ANK疗法反应良好的实体瘤有许多PD-L1阳性肿瘤细胞。由于存在许多PD-L1阳性肿瘤细胞,ANK疗法被认为对ATL有效。此外,对于NK活性降低的患者,给予活化的NK细胞可能会增加肿瘤杀伤活性。虽然还需要进一步研究,但PD-L1阳性率和NK活性可能是ANK疗法有效性的生物标志物。

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