Independent expression of circulating and tissue levels of PD-L1: correlation of clusters with tumor metabolism and outcome in patients with non-small cell lung cancer

Fabio Grizzi, Angelo Castello, Dorina Qehajaj, Luca Toschi, Sabrina Rossi, Daniela Pistillo, Valentina Paleari, Giulia Veronesi, Pierluigi Novellis, Simona Monterisi, Rossana Mineri, Daoud Rahal, Egesta Lopci

Research output: Contribution to journalArticlepeer-review

Abstract

PURPOSE: To evaluate the clinical-pathological and prognostic significance of the circulating PD-L1 level in patients with surgically treated NSCLC, by combining data for PD-L1 expression with other immune-related markers and tumor metabolism.

METHODS: Overall, 40 patients with resected NSCLC (stage Ia-IIIa) who had preoperative blood storage and underwent staging PET/CT were enrolled for the study. In all cases, we determined plasma levels of PD-L1 (pg/ml), immune-reactive areas (IRA %) covered by CD3, CD68, CD20, CD8, PD-1, and PD-L1 in the tumor specimen, and metabolic parameters on PET, i.e., SUVmax, SUVpeak, metabolic tumor volume (MTV), and total lesion glycolysis (TLG). Variables were statistically analyzed to establish their association with disease-free survival (DFS).

RESULTS: The circulating levels of PD-L1 in the bloodstream could be determined in 38/40 (95%) samples. The mean and median expression levels were 34.86 pg/ml and 24.83 pg/ml, respectively. We did not find any statistically significant correlation between circulating PD-L1 and tissue expression of PD-L1/PD-1. Some mild degree of positive correlation was determined between tissue PD-L1 and SUVmax (ρ = 0.390; p = 0.0148). Hierarchical clustering combining circulating, tissue, and metabolic parameters identified clusters with high metabolic tumor burden or high expression of plasma PD-L1 levels (Z score ≥ 2) as having a poor DFS (p = 0.033). The multivariate analysis detected stage and metabolism (i.e., SUVmax and SUVpeak) as independent prognostic factors for DFS.

CONCLUSION: Plasma levels of PD-L1 are independent of the expression of PD-1/PD-L1 in NSCLC tumor tissue and, when combined with other clinical-pathological parameters, allow for the identification of clusters with different outcomes.

Original languageEnglish
Pages (from-to)1537-1545
Number of pages9
JournalCancer Immunology and Immunotherapy
Volume68
Issue number9
DOIs
Publication statusPublished - Sep 2019

Keywords

  • Adult
  • Aged
  • Aged, 80 and over
  • B7-H1 Antigen/genetics
  • Blood Proteins/genetics
  • Carcinoma, Non-Small-Cell Lung/diagnosis
  • Female
  • Gene Expression Regulation, Neoplastic
  • Glycolysis
  • Humans
  • Lung Neoplasms/diagnosis
  • Male
  • Middle Aged
  • Neoplasm Staging
  • Prognosis
  • Survival Analysis
  • Treatment Outcome
  • Tumor Burden

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