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Cancer Immunology, Immunotherapy
Published in: Cancer Immunology, Immunotherapy 9/2019

01-09-2019 | NSCLC | Original Article

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

Authors: 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

Published in: Cancer Immunology, Immunotherapy | Issue 9/2019

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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.
Appendix
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Metadata
Title
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
Authors
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
Publication date
01-09-2019
Publisher
Springer Berlin Heidelberg
Keywords
NSCLC
NSCLC
Published in
Cancer Immunology, Immunotherapy / Issue 9/2019
Print ISSN: 0340-7004
Electronic ISSN: 1432-0851
DOI
https://doi.org/10.1007/s00262-019-02387-9

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