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结蛋白 B PET 显像在结肠癌联合化疗和免疫检查点抑制剂治疗中的应用。

Granzyme B PET Imaging of Combined Chemotherapy and Immune Checkpoint Inhibitor Therapy in Colon Cancer.

机构信息

Agency for Science, Technology and Research (A*STAR), Singapore Bioimaging Consortium, 11 Biopolis Way, #01-02 Helios, Singapore, 138667, Singapore.

Institute of Chemical and Engineering Sciences (ICES), A*STAR, 8 Biomedical Grove, #07, Neuros, Singapore, 138665, Singapore.

出版信息

Mol Imaging Biol. 2021 Oct;23(5):714-723. doi: 10.1007/s11307-021-01596-y. Epub 2021 Mar 12.

DOI:10.1007/s11307-021-01596-y
PMID:33713000
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8410722/
Abstract

PURPOSE

Chemotherapeutic adjuvants, such as oxaliplatin (OXA) and 5-fluorouracil (5-FU), that enhance the immune system, are being assessed as strategies to improve durable response rates when used in combination with immune checkpoint inhibitor (ICI) monotherapy in cancer patients. In this study, we explored granzyme B (GZB), released by tumor-associated immune cells, as a PET imaging-based stratification marker for successful combination therapy using a fluorine-18 (F)-labelled GZB peptide ([F]AlF-mNOTA-GZP).

METHODS

Using the immunocompetent CT26 syngeneic mouse model of colon cancer, we assessed the potential for [F]AlF-mNOTA-GZP to stratify OXA/5-FU and ICI combination therapy response via GZB PET. In vivo tumor uptake of [F]AlF-mNOTA-GZP in different treatment arms was quantified by PET, and linked to differences in tumor-associated immune cell populations defined by using multicolour flow cytometry.

RESULTS

[F]AlF-mNOTA-GZP tumor uptake was able to clearly differentiate treatment responders from non-responders when stratified based on changes in tumor volume. Furthermore, [F]AlF-mNOTA-GZP showed positive associations with changes in tumor-associated lymphocytes expressing GZB, namely GZB+ CD8+ T cells and GZB+ NK+ cells.

CONCLUSIONS

[F]AlF-mNOTA-GZP tumor uptake, driven by changes in immune cell populations expressing GZB, is able to stratify tumor response to chemotherapeutics combined with ICIs. Our results show that, while the immunomodulatory mode of action of the chemotherapies may be different, the ultimate mechanism of tumor lysis through release of Granzyme B is an accurate biomarker for treatment response.

摘要

目的

奥沙利铂（OXA）和 5-氟尿嘧啶（5-FU）等化疗佐剂可增强免疫系统，当与免疫检查点抑制剂（ICI）单药治疗联合用于癌症患者时，它们被评估为提高持久缓解率的策略。在这项研究中，我们通过使用氟-18（F）标记的颗粒酶 B（GZB）肽[F]AlF-mNOTA-GZP，探索了肿瘤相关免疫细胞释放的颗粒酶 B（GZB）作为基于 PET 成像的成功联合治疗分层标志物。

方法

使用免疫功能正常的 CT26 同源小鼠结肠癌模型，我们评估了[F]AlF-mNOTA-GZP 通过 GZB PET 对 OXA/5-FU 和 ICI 联合治疗反应进行分层的潜力。通过 PET 定量测量不同治疗臂中[F]AlF-mNOTA-GZP 的肿瘤摄取，并将其与使用多色流式细胞术定义的肿瘤相关免疫细胞群的差异联系起来。

结果

当根据肿瘤体积变化进行分层时，[F]AlF-mNOTA-GZP 肿瘤摄取能够清楚地区分治疗反应者和非反应者。此外，[F]AlF-mNOTA-GZP 与表达 GZB 的肿瘤相关淋巴细胞的变化呈正相关，即 GZB+CD8+T 细胞和 GZB+NK+细胞。

结论

[F]AlF-mNOTA-GZP 肿瘤摄取，由表达 GZB 的免疫细胞群变化驱动，能够对化疗联合 ICI 的肿瘤反应进行分层。我们的结果表明，虽然化疗的免疫调节作用模式可能不同，但通过释放颗粒酶 B 导致肿瘤溶解的最终机制是治疗反应的准确生物标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6e2f/8410722/53af66c7aa5c/11307_2021_1596_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6e2f/8410722/e7b2c3ca61fe/11307_2021_1596_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6e2f/8410722/66b165399ab0/11307_2021_1596_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6e2f/8410722/f1b55ebb52e3/11307_2021_1596_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6e2f/8410722/53af66c7aa5c/11307_2021_1596_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6e2f/8410722/e7b2c3ca61fe/11307_2021_1596_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6e2f/8410722/66b165399ab0/11307_2021_1596_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6e2f/8410722/f1b55ebb52e3/11307_2021_1596_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6e2f/8410722/53af66c7aa5c/11307_2021_1596_Fig4_HTML.jpg

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本文引用的文献

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2
Pseudoprogression and hyperprogression in lung cancer: a comprehensive review of literature.肺癌中的假性进展和超进展：文献综述
J Cancer Res Clin Oncol. 2020 Dec;146(12):3269-3279. doi: 10.1007/s00432-020-03360-1. Epub 2020 Aug 28.
3
Granzyme B PET Imaging of Immune Checkpoint Inhibitor Combinations in Colon Cancer Phenotypes.GrB PET 显像在免疫检查点抑制剂联合治疗结直肠癌表型中的应用。
用于评估肿瘤对免疫疗法反应的靶向颗粒酶的猝灭型基于活性的探针。
bioRxiv. 2025 Mar 15:2025.03.13.643086. doi: 10.1101/2025.03.13.643086.
4
Current status and future prospects of molecular imaging in targeting the tumor immune microenvironment.分子成像在靶向肿瘤免疫微环境中的现状与未来前景
Front Immunol. 2025 Jan 22;16:1518555. doi: 10.3389/fimmu.2025.1518555. eCollection 2025.
5
PET Imaging for Monitoring Cellular and Immunotherapy of Cancer.正电子发射断层扫描成像用于监测癌症的细胞和免疫治疗。
Cancer J. 2024;30(3):153-158. doi: 10.1097/PPO.0000000000000722.
6
Advances in PET imaging of cancer.癌症正电子发射断层成像技术的进展。
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7
Colon Cancer Diagnosis Based on Machine Learning and Deep Learning: Modalities and Analysis Techniques.基于机器学习和深度学习的结肠癌诊断：模态分析和技术。
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8
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