New insight on the correlation of metabolic status on 18F-FDG PET/CT with immune marker expression in patients with non-small cell lung cancer.

Abstract

Metabolic information obtained through 18F-flurodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) is used to evaluate malignancy by calculating the glucose uptake rate, and these parameters play important roles in determining the prognosis of non-small cell lung cancer (NSCLC). The expression of immune-related markers in tumor tissue reflects the immune status in the tumor microenvironment. However, there is lack of reports on the association between metabolic variables and intra-tumor immune markers. Herein, we investigate the correlation between metabolic status on 18F-FDG PET/CT and intra-tumor immunomarkers' expression in NSCLC patients. From April 2008 to August 2014, 763 patients were enrolled in the analysis to investigate the role of maximum standardized uptake value (SUVmax) in lung cancer. One hundred twenty-two tumor specimens were analyzed by immunohistochemistry (IHC) to intra-tumor immune cells and programmed death protein ligand 1(PD-L1) expression on tumor cells. The correlation between metabolic variables and the expression of tissue immune markers were analyzed. SUVmax values have significant variations in different epidermal growth factor receptor (EGFR) statuses (wild type vs mutant type), high/low neutrophil-to-lymphocyte ratio (NLR) groups, and high/low platelets-to-lymphocyte ratio (PLR) groups (p < 0.001, p < 0.001, p = 0.003, respectively). SUVmax was an independent prognostic factor in lung cancer patients (p = 0.013). IHC demonstrated a statistically significant correlation between SUVmax and the expression of CD8 tumor-infiltrating lymphocytes (p = 0.015), CD163 tumor-associated macrophages (TAMs) (p = 0.003), and Foxp3-regulatory T cells (Tregs) (p = 0.004), as well as PD-1 and PD-L1 (p = 0.003 and p = 0.012, respectively). With respect to patient outcomes, disease stage, BMI, SUVmax, metabolic tumor volume (MTV), TLG (tumor lesion glycolysis), CD163-TAMs, CD11c-dendritic cells (DCs), PD-L1, and Tregs showed a statistically significant correlation with progression-free survival (PFS) (p < 0.001, 0.023, < 0.001, 0.007, 0.005, 0.004, 0.008, 0.048, and 0.014, respectively), and disease stage, SUVmax, MTV, TLG, CD163-TAMs, CD11c-DCs, and PD-L1 showed a statistically significant correlation with overall survival (OS) (p < 0.001, < 0.001, 0.014, 0.012, < 0.001, 0.001, and < 0.001, respectively). This study revealed an association between metabolic variable and immune cell expression in the tumor microenvironment and suggests that SUVmax on 18F-FDG PET/CT could be a potential predictor for selecting candidates for immunotherapy.