Correlation of tumor-related immunity with 18F-FDG-PET in pulmonary squamous-cell carcinoma

Lung Cancer. 2018 May:119:71-77. doi: 10.1016/j.lungcan.2018.03.001. Epub 2018 Mar 16.

Abstract

Objectives: 2-Deoxy-2-[fluorine-18] fluoro-d-glucose with positron emission tomography (18F-FDG-PET) is a clinically useful tool for cancer evaluation. 18F-FDG accumulation in tumor cells is known to be correlated with the presence of glucose transporter 1 (GLUT1) and hypoxia-inducible factor-1α (HIF-1α). Although anti-programmed death-1 (PD-1) antibody treatments have been approved, no suitable predictor of significant responders has been identified. Based on the existing information, we investigated the relationship between tumor immunity (including PD-L1) and 18F-FDG uptake in patients with surgically resected pulmonary squamous-cell carcinoma (SQC).

Materials and methods: This study included 167 patients (153 men and 14 women) with SQC who underwent 18F-FDG PET. Tumor sections were stained by immunohistochemistry for GLUT1, HIF-1α, PD-L1, CD4, CD8, and Foxp3. The relationship between clinicopathological features and 18F-FDG uptake was analyzed. Student's t-test, the χ2 test, non-parametric Spearman's rank test and the Kaplan-Meier method were used to show associations between variables.

Results: The rate of positive PD-L1 expression was 79% (132/167), and PD-L1 expression was significantly associated with GLUT1 (P < 0.01), HIF-1α (P < 10-4), and CD8 (P < 1 × 10-3) expression. The SUVmax of 18F-FDG was significantly correlated with PD-L1 (P = 0.02) and GLUT1 (P < 0.01) expression. Multivariate analysis demonstrated that advanced stage, elevated PD-L1 expression, and elevated SUVmax were independent prognostic factors for predicting poor OS. Among patients with a high SUVmax, multivariate analysis confirmed that advanced stage and high PD-L1 expression were independent prognostic factors for poor OS; however, there was no significant difference among patients with a low SUVmax.

Conclusion: High SUVmax on 18F-FDG-PET is associated with PD-L1 expression but is an independent prognostic factor for OS in our population of surgically resected pulmonary squamous-cell carcinoma.

Keywords: (18)F-FDG-PET; GLUT1; HIF-1; Lung cancer; PD-L1; Squamous-cell carcinoma.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • B7-H1 Antigen / metabolism
  • CD8-Positive T-Lymphocytes / immunology*
  • Carcinoma, Squamous Cell / diagnosis
  • Carcinoma, Squamous Cell / immunology*
  • Carcinoma, Squamous Cell / mortality
  • Female
  • Fluorodeoxyglucose F18
  • Forkhead Transcription Factors / metabolism
  • Glucose Transporter Type 1 / metabolism
  • Humans
  • Hypoxia-Inducible Factor 1, alpha Subunit / metabolism
  • Immunity
  • Lung Neoplasms / diagnosis
  • Lung Neoplasms / immunology*
  • Lung Neoplasms / mortality
  • Male
  • Middle Aged
  • Positron-Emission Tomography
  • Survival Analysis
  • T-Lymphocytes, Regulatory / immunology*

Substances

  • B7-H1 Antigen
  • CD274 protein, human
  • FOXP3 protein, human
  • Forkhead Transcription Factors
  • Glucose Transporter Type 1
  • HIF1A protein, human
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • Fluorodeoxyglucose F18