Diagnostic value of 18F-FDG-PET to predict the tumour immune status defined by tumoural PD-L1 and CD8+tumour-infiltrating lymphocytes in oral squamous cell carcinoma

Abstract

BACKGROUND: Lately, immune checkpoint proteins, such as programmed death 1 (PD-1) and its ligand-1 (PD-L1), have garnered attention as a new target in oral squamous cell carcinoma (OSCC). Reportedly, fluoro-D-glucose (FDG)-uptake alteration by anti-PD-1 antibody treatment depicts the response in patients with lung cancer. This study aims to elucidate the correlations between tumour immune status, clinicopathological factors, 18 F-FDG-uptake and cold tumour phenotypes as low PD-L1 expression/low CD8 + tumour-infiltrating lymphocytes (TILs) in OSCC. METHODS: We performed immunohistochemical analysis of PD-L1, hypoxia-inducible factor 1 A (HIF-1A), glucose transporter type 1 (GLUT1), CD8, E-cadherin and Ki-67 on 59 operable OSCC samples. We assessed the correlations between these factors and preoperative 18 F-FDG-uptake, clinicopathological characteristics and prognosis. RESULTS: Low expression of PD-L1 in OSCC correlated with cancer aggressiveness, poor prognosis, high 18 F-FDG-uptake with HIF-1A/GLUT1 and low E-cadherin expression and low CD8. Cold tumour phenotypes as low PD-L1 tumour cells and low stromal CD8 correlated with the poor prognosis, high 18 F-FDG-uptake and E-cadherin suppression. Furthermore, the high level of preoperative 18 F-FDG-uptake in OSCC was an independent predictor of the cold tumour immune status. CONCLUSIONS: 18 F-FDG-uptake is an independent predictor of cold tumour in OSCC. 18 F-FDG-PET imaging could be a promising diagnostic tool to estimate tumour immune status.

Obesity is a risk factor for intrahepatic cholangiocarcinoma progression associated with alterations of metabolic activity and immune status

“…Furthermore, adipocytes are associated with systemic hypoxia and cancer progression in the tumor microenvironment (TME) 34 . Several studies demonstrated that HIF-1A/GLUT1 signaling is related to 18 F-FDG uptake among patients with cancer and metabolic disorder 18 , 35 . Moreover, glucose metabolism in tumor cells has been reported to play crucial roles in tumor progression by regulating local tumor immunity 36 .…”

ImmunoPET imaging of human CD8+ T cells with novel 68Ga-labeled nanobody companion diagnostic agents

“…However, the most commonly used detection methods such as flow cytometry for blood samples and immunohistochemistry for tissue biopsy fail to provide comprehensive and dynamic information and have certain limitations. Moreover, it is challenging for 18 F-FDG to distinguish between pseudoprogression and immune-related adverse events [ 22 , 23 ]. ImmunoPET will provide great help for precisely stratifying patients into responders and nonresponders before treatment, and determining to continue or terminate therapy during the process or even predicting the patient outcome by tracking CD8 + T cells.…”

Relationship between tumor mutational burden and maximum standardized uptake value in 2-[18F]FDG PET (positron emission tomography) scan in cancer patients

“…Prior studies have investigated the complex relationship between tumor immune microenvironment and glucose metabolism rate and shown associations between metabolic and immune profiles [ 15 , 16 ]. 2-[ 18 F]FDG PET imaging has been suggested as a diagnostic tool to estimate tumor immune status [ 17 ]. Our hypothesis was that higher mutational load (as reflected by TMB) might correlate with metabolic reconfiguration [ 18 ], and immune inflammatory response [ 12 ], and that either of these features would be associated with a higher SUV max [ 19 ].…”