Correlation of metabolic information on FDG-PET with tissue expression of immune markers in patients with non-small cell lung cancer (NSCLC) who are candidates for upfront surgery

Egesta Lopci, Luca Toschi, Fabio Grizzi, Daoud Rahal, Laura Olivari, Giovanni Francesco Castino, Silvia Marchetti, Nina Cortese, Dorina Qehajaj, Daniela Pistillo, Marco Alloisio, Massimo Roncalli, Paola Allavena, Armando Santoro, Federica Marchesi, Arturo Chiti

Research output: Contribution to journalArticlepeer-review


Purpose: Eliciting antitumor T-cell response by targeting the PD-1/PD-L1 axis with checkpoint inhibitors has emerged as a novel therapeutic strategy in non-small cell lung cancer (NSCLC). The identification of predictors for sensitivity or resistance to these agents is, therefore, needed. Herein, we investigate the correlation of metabolic information on FDG-PET with tissue expression of immune-checkpoints and other markers of tumor-related immunity in resected NSCLC patients. Materials and methods: All patients referred to our institution for upfront surgical resection of NSCLC, who were investigated with FDG-PET prior to surgery, were consecutively included in the study. From January 2010 to May 2014, 55 patients (stage IA-IIIB; M:F = 42:13; mean age 68.9 years) were investigated. Sampled surgical tumor specimens were analyzed by immunohistochemistry (IHC) for CD68-TAMs (tumor-associated macrophages), CD8-TILs (tumor infiltrating lymphocytes), PD-1-TILs, and PD-L1 tumor expression. Immunoreactivity was evaluated, and scores were compared with imaging findings. FDG-PET images were analyzed to define semi-quantitative parameters: SUVmax and SUVmean. Metabolic information on FDG-PET was correlated with tissue markers expression and disease-free survival (DFS) considering a median follow-up of 16.2 months. Results: Thirty-six adenocarcinomas (ADC), 18 squamous cell carcinomas (SCC), and one sarcomatoid carcinoma were analyzed. All tumors resulted positive at FDG-PET: median SUVmax 11.3 (range: 2.3–32.5) and SUVmean 6.4 (range: 1.5–13) both resulted significantly higher in SCC compared to other NSCLC histotypes (p = 0.007 and 0.048, respectively). IHC demonstrated a median immunoreactive surface covered by CD68-TAMs of 5.41 % (range: 0.84–14.01 %), CD8-TILs of 2.9 % (range: 0.11–11.92 %), PD-1 of 0.65 % (range: 0.02–5.87 %), and PD-L1 of 0.7 % (range: 0.03–10.29 %). We found a statistically significant correlation between SUVmax and SUVmean with the expression of CD8 TILs (rho = 0.31; p = 0.027) and PD-1 (rho = 0.33; p = 0.017 and rho = 0.36; p = 0.009, respectively). The other tissue markers correlated as follows: CD8 TILs and PD-1 (rho = 0.45; p = 0.001), CD8 TILs and PD-L1 (rho = 0.41; p = 0.003), CD68-TAMs and PD-L1 (rho = 0.30; p = 0.027), PD-1 and PD-L1 (rho = 0.26; p = 0.059). With respect to patients’ outcome, SUVmax, SUVmean, and disease stage showed a statistically significant correlation with DFS (p = 0.002, 0.004, and

Original languageEnglish
Pages (from-to)1-8
Number of pages8
JournalEuropean Journal of Nuclear Medicine and Molecular Imaging
Publication statusAccepted/In press - Jun 1 2016


  • Immunometabolism
  • PD-L1
  • TAMs
  • TILs
  • Tumor-related immunity

ASJC Scopus subject areas

  • Radiology Nuclear Medicine and imaging


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