WNT/β-catenin Signaling and CD8+ Tumor-infiltrating Lymphocytes in Tremelimumab Plus Durvalumab for Advanced Hepatocellular Carcinoma.

IF 1.8 4区医学 Q3 MEDICINE, RESEARCH & EXPERIMENTAL

In vivo Pub Date : 2024-11-01 DOI:10.21873/invivo.13757

Akifumi Kuwano, Kosuke Tanaka, Junro Takahira, Hideo Suzuki, Yoshihiro Ohishi, Kenta Motomura

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引用次数: 0

Abstract

Background/aim: Tremelimumab plus durvalumab is an approved first-line therapy for advanced hepatocellular carcinoma (HCC). Previous studies identified WNT/β-catenin mutations or CD8+ tumor-infiltrating lymphocytes (TILs) as biomarkers that can predict responsiveness to immune checkpoint inhibitor therapy in HCC. However, biomarkers for effectiveness of tremelimumab plus durvalumab in HCC have not been reported. This study investigated whether evaluation of WNT/β-catenin signaling and CD8+ TILs by immunohistochemical staining of tumor biopsy tissues can predict the response to tremelimumab plus durvalumab in patients with HCC.

Patients and methods: Fifteen HCC patients who underwent tumor biopsies were classified into three groups based on WNT/β-catenin signal activation and CD8+ TIL infiltration. The clinical responses to treatment in the groups were evaluated.

Results: Four patients had HCC with WNT/β-catenin signal inactivation and high-level CD8+ TIL infiltration, four patients had HCC with WNT/β-catenin signal activation and low-level CD8+ TIL infiltration, and seven patients had WNT/β-catenin signal activation and high-level CD8+ TIL infiltration or WNT/β-catenin signal inactivation and low-level CD8+ TIL infiltration. A better response rate was observed in the WNT/β-catenin signal inactivation and high-level CD8+ TIL infiltration group, and a worse response rate was observed in the WNT/β-catenin signal activation and low-level CD8+ TIL infiltration group.

Conclusion: Although the present study involved a small number of patients, the findings suggest that the efficacy of tremelimumab plus durvalumab may be affected by WNT/β-catenin signaling and CD8+ TIL infiltration.

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WNT/β-catenin信号传导与CD8+肿瘤浸润淋巴细胞在特瑞莫司单抗加Durvalumab治疗晚期肝细胞癌中的作用

背景/目的：特雷莫单抗加杜瓦单抗是一种已获批准的晚期肝细胞癌（HCC）一线疗法。先前的研究发现，WNT/β-catenin突变或CD8+肿瘤浸润淋巴细胞（TILs）是可以预测HCC对免疫检查点抑制剂治疗反应性的生物标志物。然而，有关曲妥木单抗加杜伐单抗治疗HCC疗效的生物标志物尚未见报道。本研究探讨了通过对肿瘤活检组织进行免疫组化染色评估WNT/β-catenin信号传导和CD8+ TILs能否预测HCC患者对曲妥木单抗联合度伐单抗的反应：根据WNT/β-catenin信号激活情况和CD8+ TIL浸润情况，将15名接受肿瘤活检的HCC患者分为三组。对各组的临床治疗反应进行了评估：结果：4例患者的HCC伴有WNT/β-catenin信号失活和高水平CD8+ TIL浸润，4例患者的HCC伴有WNT/β-catenin信号激活和低水平CD8+ TIL浸润，7例患者伴有WNT/β-catenin信号激活和高水平CD8+ TIL浸润或WNT/β-catenin信号失活和低水平CD8+ TIL浸润。WNT/β-catenin信号失活和高水平CD8+ TIL浸润组的反应率较好，而WNT/β-catenin信号激活和低水平CD8+ TIL浸润组的反应率较差：结论：尽管本研究涉及的患者人数较少，但研究结果表明，WNT/β-catenin信号激活和CD8+ TIL浸润可能会影响曲妥珠单抗联合度伐单抗的疗效。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

In vivo 医学-医学：研究与实验

CiteScore

4.20

自引率

4.30%

发文量

330

审稿时长

3-8 weeks

期刊介绍： IN VIVO is an international peer-reviewed journal designed to bring together original high quality works and reviews on experimental and clinical biomedical research within the frames of physiology, pathology and disease management. The topics of IN VIVO include: 1. Experimental development and application of new diagnostic and therapeutic procedures; 2. Pharmacological and toxicological evaluation of new drugs, drug combinations and drug delivery systems; 3. Clinical trials; 4. Development and characterization of models of biomedical research; 5. Cancer diagnosis and treatment; 6. Immunotherapy and vaccines; 7. Radiotherapy, Imaging; 8. Tissue engineering, Regenerative medicine; 9. Carcinogenesis.