Dataset Information

PET/CT Imaging of Activated Cancer-Associated Fibroblasts Predict Response to PD-1 Blockade in Gastric Cancer Patients.

ABSTRACT:

Background

Promising development in immune checkpoint blockade (ICB) therapy has shown remarkable results in the treatment of gastric cancer (GC). However, the objective response rate in GC remains unsatisfactory. Noninvasive imaging to predict responses to ICB therapy via tumor microenvironment (TME) assessment is needed. Accordingly, this study aimed to evaluate the role of ⁶⁸Ga-FAPI-04 PET/CT in the assessment of the immunosuppressive TME in GC and to cross-correlate imaging findings with responses to ICB therapy.

Methods

The correlation between fibroblast-activation-protein (FAP) expression and immunosuppressive cell infiltration was analyzed using The Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO) database, and GC tissue microarrays. To characterize the TME, TMEscores were calculated based on RNA-seq data from four GC patients. A total of 21 patients with GC underwent ⁶⁸Ga-FAPI-04 PET/CT before ICB treatment, and two of them were imaged after ICB therapy.

Results

FAP expression was found to be closely correlated with poor prognosis and infiltration of immunosuppressive cells, including myeloid-derived suppressor cells (MDSCs), exhausted T cells, and regulatory T cells (Tregs) in GC. We also found a strong relationship (R ² = 0.9678, p = 0.0162) between ⁶⁸Ga-FAPI-04 uptake and TMEscore. Further analyses indicated that high ⁶⁸Ga-FAPI-04 uptake was correlated with reduced therapeutic benefits from ICB therapy.

Conclusions

⁶⁸Ga-FAPI-04 PET/CT may be used to noninvasively image the cancer-associated fibroblasts immunosuppressive TME in vivo and also potentially serve as a predictive biomarker of survival and antitumor immune response among patients who received ICB therapies.

SUBMITTER: Rong X

PROVIDER: S-EPMC8825781 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature

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Publications

PET/CT Imaging of Activated Cancer-Associated Fibroblasts Predict Response to PD-1 Blockade in Gastric Cancer Patients.

Rong Xiaoxiang X Lv Jinyu J Liu Yantan Y Wang Zhaojun Z Zeng Dongqiang D Li Yuedan Y Li Shaowei S Wu Jianhua J Shen Zheyu Z Shi Min M Liao Wangjun W Wu Zhenzhen Z Wang Chunlin C

Frontiers in oncology 20220126

<h4>Background</h4>Promising development in immune checkpoint blockade (ICB) therapy has shown remarkable results in the treatment of gastric cancer (GC). However, the objective response rate in GC remains unsatisfactory. Noninvasive imaging to predict responses to ICB therapy <i>via</i> tumor microenvironment (TME) assessment is needed. Accordingly, this study aimed to evaluate the role of <sup>68</sup>Ga-FAPI-04 PET/CT in the assessment of the immunosuppressive TME in GC and to cross-correlate ...[more]

PMID: 35155199

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Project description:PurposeThe role of hybrid imaging using 18F-fluoro-2-deoxy-D-glucose positron-emission tomography (FDG-PET), computed tomography (CT) and magnetic resonance imaging (MRI) to improve preoperative evaluation of rectal cancer is largely unknown. To investigate this, the RECTOPET (REctal Cancer Trial on PET/MRI/CT) study has been launched with the aim to assess staging and restaging of primary rectal cancer. This report presents the study workflow and the initial experiences of the impact of PET/CT on staging and management of the first patients included in the RECTOPET study.MethodsThis prospective cohort study, initiated in September 2016, is actively recruiting patients from Region Västerbotten in Sweden. This pilot study includes patients recruited and followed up until December 2017. All patients had a biopsy-verified rectal adenocarcinoma and underwent a minimum of one preoperative FDG-PET/CT and FDG-PET/MRI examination. These patients were referred to the colorectal cancer multidisciplinary team meeting at Umeå University Hospital. All available data were evaluated when making management recommendations. The clinical course was noted and changes consequent to PET imaging were described; surgical specimens underwent dedicated MRI for anatomical matching between imaging and histopathology.ResultsTwenty-four patients have so far been included in the study. Four patients were deemed unresectable, while 19 patients underwent or were scheduled for surgery; one patient was enrolled in a watch-and-wait programme after restaging. Consequent to taking part in the study, two patients were upstaged to M1 disease: one patient was diagnosed with a solitary hepatic metastasis detected using PET/CT and underwent metastasectomy prior to rectal cancer surgery, while one patient with a small, but metabolically active, lung nodulus experienced no change of management. PET/MRI did not contribute to any recorded change in patient management.ConclusionsThe RECTOPET study investigating the role of PET/CT and PET/MRI for preoperative staging of primary rectal cancer patients will provide novel data that clarify the value of adding hybrid to conventional imaging, and the role of PET/CT versus PET/MRI.Trial registrationNCT03846882 .

Dataset Information

PET/CT Imaging of Activated Cancer-Associated Fibroblasts Predict Response to PD-1 Blockade in Gastric Cancer Patients.

Background

Methods

Results

Conclusions

Publications

PET/CT Imaging of Activated Cancer-Associated Fibroblasts Predict Response to PD-1 Blockade in Gastric Cancer Patients.

Similar Datasets

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