Correlation of PD-L1 expression on tumor cell and tumor infiltrating immune cell with 18F-fluorodeoxyglucose uptake on PET/computed tomography in surgically resected pulmonary adenocarcinoma

Abstract

Objective The uptake of 18F-fluorodeoxyglucose (18F-FDG) PET/computed tomography (CT) is known to be linked to programmed death ligand 1 (PD-L1) expression on tumor cells (TC). However, the association between PD-L1 expression on immune cells (IC) and 18F-FDG accumulation is still unclear. Here, we conducted a clinicopathological study to investigate the relationship between PD-L1 expression on TC/IC and 18F-FDG uptake in patients with surgically resected pulmonary adenocarcinoma (ADC). Methods A total of 450 ADC patients who underwent preoperative 18F-FDG-PET/CT imaging were analyzed retrospectively. Immunohistochemistry analysis was performed for PD-L1 expression on TC and IC in ADC specimens with SP142. PD-L1 expression was performed on whole-tissue sections and given scores (0/1/2/3) according to percent of PD-L1+ cells in TC and IC. Results Compared to TC0 and IC0, PD-L1 positive expression was 90.4% (407/450) in ADC specimens. Both PD-L1 expression score on TC and IC were associated with maximum standardized uptake (SUVmax). SUVmax augmented with increasing PD-L1 expression (TC0 and IC0, 4.3 ± 3.4; TC or IC1/2/3, 7.7 ± 5.6; TC or IC2/3, 8.1 ± 5.6; TC or IC3, 8.4 ± 5.4). The best cut-off value of PD-L1 expression, determined by receiver operating characteristic curve, was 5.1 for TC or IC1/2/3 [area under the curve (AUC) = 0.713, sensitivity 62.2%, specificity 72.1%]. Multivariate analysis demonstrated that TC or IC1/2/3 subset was correlated with histological subtype, PD-1 expression on IC and SUVmax. Conclusion High SUVmax is associated with PD-L1 expression on TC and IC in surgically resected pulmonary ADC. 18F-FDG-PET/CT imaging can be a potential tool to evaluate PD-L1 expression in pulmonary ADC.

Predictive value of 18F‐fluorodeoxyglucose positron emission tomography/computed tomography for PD‐L1 expression in non‐small cell lung cancer: A systematic review and meta‐analysis

“…The remaining seven full text articles were assessed for eligibility and one article was excluded due to insufficient data for the calculation of sensitivity and specificity of 18F‐FDG PET or PET/CT for the prediction of PD‐L1 expression in NSCLC patients. Finally, six studies were selected that were eligible for systematic review and meta‐analysis and no additional studies were found screening the references of these articles 22–27 . The characteristics of the included studies are presented in Table 1.…”

“…Also, studies included in this meta‐analysis used different definition for positivity of PD‐L1 protein expression. Four studies used the cutoff value of 5% for defining PD‐L1 positivity 23–25, 27 and another two studies used 1% for positivity 22, 26 . Immunohistochemical analysis were performed using different methods to determine PD‐L1 expression.…”

“…Four studies used the cutoff value of 5% for defining PD-L1 positivity [23][24][25]27 and another two studies used 1% for positivity. 22,26 Immunohistochemical analysis were performed using different methods to determine PD-L1 expression. Different PD-L1 monoclonal antibodies from different vendors (clone SP 142, dilution 1:100; Spring Bioscience, Ventana, Arizona, USA), 24,25 (clone SP 142, dilution 1:300; OriGene Technologies, Maryland, USA), 21 (clone 28-8, Abcam, Cambridge, UK), 27 and (clone 28-8, pharmDx, California, USA) 23 were used in the studies.…”

“…Finally, six studies were selected that were eligible for systematic review and meta-analysis and no additional studies were found screening the references of these articles. [22][23][24][25][26][27] The characteristics of the included studies are presented in Table 1. The detailed procedure of study selection in the current meta-analysis is shown in Fig 1. Study description, quality, and publication bias…”

“…Four studies were from China. 22,23,26,27 A further two studies were performed by Non-China investigators. 24,25 The median prevalence of PD-L1 (+) of the six studies included was 37.15% with a range of 9.6% to 70.8%.…”