Background: 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.
Methods: 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.
Results: 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).
Conclusion: 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.
Keywords: 18F-FDG PET/CT; Immunomarkers; Non-small cell lung cancer; Prognosis; Standardized uptake value.