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 i...

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Bibliographic Details
Published in:Molecular imaging 2021, Vol.2021, p.9305277-9305277
Main Authors: Goggi, Julian L., Ramasamy, Boominathan, Tan, Yun Xuan, Hartimath, Siddesh V., Tang, Jun Rong, Cheng, Peter, Msallam, Rasha, Chacko, Ann-Marie, Hwang, You Yi, Robins, Edward G.
Format: Article
Language:English
Subjects:
Biomarkers
Cancer
CD4 antigen
Flow cytometry
Fluorine isotopes
Granzyme B
Hepatocellular carcinoma
Immune checkpoint inhibitors
Immune response
Immune system
Immunoregulation
Liver cancer
Lymphocytes T
Medical imaging
Pharmaceuticals
Positron emission
Radiochemistry
Radioisotopes
Retention
Therapy
Tumor microenvironment
Tumors
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Summary: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.
ISSN:1536-0121
1535-3508
1536-0121
DOI:10.1155/2021/9305277