Institute of Bioengineering and Bioimaging, Agency for Science, Technology and Research (ASTAR), 11 Biopolis Way, #01-02 Helios, Singapore 138667.
Laboratory for Translational and Molecular Imaging (LTMI), Cancer and Stem Cell Biology Programme, Duke-NUS Medical School, 8 College Road, Singapore 169857.
Mol Imaging. 2021 Dec 9;2021:9305277. doi: 10.1155/2021/9305277. eCollection 2021.
Hepatocellular carcinoma (HCC) is a notoriously difficult cancer to treat. The recent development of immune checkpoint inhibitors has revolutionised HCC therapy; however, successful response is only observed in a small percentage of patients. Biomarkers typically used to predict treatment response in other tumour types are ineffective in HCC, which arises in an immune-suppressive environment. However, imaging markers that measure changes in tumour infiltrating immune cells may supply information that can be used to determine which patients are responding to therapy posttreatment. We have evaluated [F]AlF-mNOTA-GZP, a radiolabeled peptide targeting granzyme B, to stratify response to ICIs in a HEPA 1-tumours, a syngeneic model of HCC. Posttherapy, tumour retention of [F]AlF-mNOTA-GZP was correlated to changes in tumour volume and tumour-infiltrating immune cells. [F]AlF-mNOTA-GZP successfully stratified response to immune checkpoint inhibition in the syngeneic HEPA 1-6 model. FACS indicated significant changes in the immune environment including a decrease in immune suppressive CD4+ T regulatory cells and increases in tumour-associated GZB+ NK+ cells, which correlated well with tumour radiopharmaceutical uptake. While the immune response to ICI therapies differs in HCC compared to many other cancers, [F]AlF-mNOTA-GZP retention is able to stratify response to ICI therapy associated with tumour infiltrating GZB+ NK+ cells in this complex tumour microenvironment.
肝细胞癌(HCC)是一种治疗难度极大的癌症。免疫检查点抑制剂的最新发展彻底改变了 HCC 的治疗方法;然而,只有一小部分患者观察到成功的反应。在 HCC 中,通常用于预测其他肿瘤类型治疗反应的生物标志物无效,因为 HCC 发生在免疫抑制环境中。然而,测量肿瘤浸润免疫细胞变化的成像标志物可能提供可用于确定哪些患者在治疗后对治疗有反应的信息。我们评估了 [F]AlF-mNOTA-GZP,一种针对颗粒酶 B 的放射性标记肽,以分层分析 HEPA 1-肿瘤(HCC 的同基因模型)中对 ICI 的反应。治疗后,[F]AlF-mNOTA-GZP 在肿瘤中的保留与肿瘤体积和肿瘤浸润免疫细胞的变化相关。[F]AlF-mNOTA-GZP 成功地对同基因 HEPA 1-6 模型中的免疫检查点抑制作用进行了分层。FACS 表明免疫环境发生了显著变化,包括免疫抑制性 CD4+T 调节细胞减少和肿瘤相关 GZB+NK+细胞增加,这与肿瘤放射性药物摄取密切相关。尽管 HCC 对 ICI 治疗的免疫反应与许多其他癌症不同,但[F]AlF-mNOTA-GZP 的保留能够分层分析与肿瘤浸润 GZB+NK+细胞相关的 ICI 治疗反应,在这种复杂的肿瘤微环境中。
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