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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| Format: | Article |
| Language: | English |
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SAGE Publishing
2021-01-01
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| Series: | Molecular Imaging |
| Online Access: | http://dx.doi.org/10.1155/2021/9305277 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Julian L. Goggi |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-80a593fefbf7406eb9f2970c1f86d7e6 |
| institution | Kabale University |
| issn | 1536-0121 |
| language | English |
| publishDate | 2021-01-01 |
| publisher | SAGE Publishing |
| record_format | Article |
| series | Molecular Imaging |
| spelling | doaj-art-80a593fefbf7406eb9f2970c1f86d7e62025-01-03T00:10:39ZengSAGE PublishingMolecular Imaging1536-01212021-01-01202110.1155/2021/9305277Granzyme B PET Imaging Stratifies Immune Checkpoint Inhibitor Response in Hepatocellular CarcinomaJulian L. Goggi0Boominathan Ramasamy1Yun Xuan Tan2Siddesh V. Hartimath3Jun Rong Tang4Peter Cheng5Rasha Msallam6Ann-Marie Chacko7You Yi Hwang8Edward G. Robins9Institute of Bioengineering and BioimagingInstitute of Bioengineering and BioimagingInstitute of Bioengineering and BioimagingInstitute of Bioengineering and BioimagingInstitute of Bioengineering and BioimagingInstitute of Bioengineering and BioimagingLaboratory for Translational and Molecular Imaging (LTMI)Laboratory for Translational and Molecular Imaging (LTMI)Singapore Immunology NetworkInstitute of Bioengineering and BioimagingHepatocellular 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.http://dx.doi.org/10.1155/2021/9305277 |
| spellingShingle | 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 Granzyme B PET Imaging Stratifies Immune Checkpoint Inhibitor Response in Hepatocellular Carcinoma Molecular Imaging |
| title | Granzyme B PET Imaging Stratifies Immune Checkpoint Inhibitor Response in Hepatocellular Carcinoma |
| title_full | Granzyme B PET Imaging Stratifies Immune Checkpoint Inhibitor Response in Hepatocellular Carcinoma |
| title_fullStr | Granzyme B PET Imaging Stratifies Immune Checkpoint Inhibitor Response in Hepatocellular Carcinoma |
| title_full_unstemmed | Granzyme B PET Imaging Stratifies Immune Checkpoint Inhibitor Response in Hepatocellular Carcinoma |
| title_short | Granzyme B PET Imaging Stratifies Immune Checkpoint Inhibitor Response in Hepatocellular Carcinoma |
| title_sort | granzyme b pet imaging stratifies immune checkpoint inhibitor response in hepatocellular carcinoma |
| url | http://dx.doi.org/10.1155/2021/9305277 |
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