颗粒酶B PET成像对肝细胞癌免疫检查点抑制剂反应的分层研究。

IF 4.6 Q2 MATERIALS SCIENCE, BIOMATERIALS
ACS Applied Bio Materials Pub Date : 2021-12-09 eCollection Date: 2021-01-01 DOI:10.1155/2021/9305277
Julian L Goggi, Boominathan Ramasamy, Yun Xuan Tan, Siddesh V Hartimath, Jun Rong Tang, Peter Cheng, Rasha Msallam, Ann-Marie Chacko, You Yi Hwang, Edward G Robins
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引用次数: 2

摘要

肝细胞癌(HCC)是一种众所周知的难以治疗的癌症。免疫检查点抑制剂的最新发展彻底改变了HCC治疗;然而,成功的反应仅在一小部分患者中观察到。通常用于预测其他肿瘤类型治疗反应的生物标志物在HCC中无效,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记可能提供信息,可用于确定哪些患者对治疗后的治疗有反应。我们已经评估了[18F]AlF-mNOTA-GZP,一种靶向颗粒酶B的放射性标记肽,在HEPA - 1肿瘤(HCC的同基因模型)中对ICIs的分层反应。治疗后,[18F]AlF-mNOTA-GZP的体内肿瘤滞留与肿瘤体积和肿瘤浸润免疫细胞的变化相关。[18F]AlF-mNOTA-GZP在同基因HEPA 1-6模型中成功分层免疫检查点抑制反应。FACS显示免疫环境发生显著变化,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。虽然与许多其他癌症相比,HCC对ICI治疗的免疫反应不同,[18F]在这种复杂的肿瘤微环境中,AlF-mNOTA-GZP保留能够分层对与肿瘤浸润GZB+ NK+细胞相关的ICI治疗的反应。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Granzyme B PET Imaging Stratifies Immune Checkpoint Inhibitor Response in Hepatocellular Carcinoma.

Granzyme B PET Imaging Stratifies Immune Checkpoint Inhibitor Response in Hepatocellular Carcinoma.

Granzyme B PET Imaging Stratifies Immune Checkpoint Inhibitor Response in Hepatocellular Carcinoma.

Granzyme B PET Imaging Stratifies Immune Checkpoint Inhibitor Response in Hepatocellular Carcinoma.

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 [18F]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, in vivo tumour retention of [18F]AlF-mNOTA-GZP was correlated to changes in tumour volume and tumour-infiltrating immune cells. [18F]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, [18F]AlF-mNOTA-GZP retention is able to stratify response to ICI therapy associated with tumour infiltrating GZB+ NK+ cells in this complex tumour microenvironment.

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来源期刊
ACS Applied Bio Materials
ACS Applied Bio Materials Chemistry-Chemistry (all)
CiteScore
9.40
自引率
2.10%
发文量
464
期刊介绍: ACS Applied Bio Materials is an interdisciplinary journal publishing original research covering all aspects of biomaterials and biointerfaces including and beyond the traditional biosensing, biomedical and therapeutic applications. The journal is devoted to reports of new and original experimental and theoretical research of an applied nature that integrates knowledge in the areas of materials, engineering, physics, bioscience, and chemistry into important bio applications. The journal is specifically interested in work that addresses the relationship between structure and function and assesses the stability and degradation of materials under relevant environmental and biological conditions.
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