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PD-1/PD-L1 immune-checkpoint blockade induces immune effector cell modulation in metastatic non-small cell lung cancer patients: A single-cell flow cytometry approach

Authors :
Antonella Fameli
Valerio Nardone
Mojtaba Shekarkar Azgomi
Giovanna Bianco
Claudia Gandolfo
Bianca Maria Oliva
Marika Monoriti
Rita Emilena Saladino
Antonella Falzea
Caterina Romeo
Natale Daniele Calandruccio
Domenico Azzarello
Rocco Giannicola
Luigi Pirtoli
Antonio Giordano
Pierfrancesco Tassone
Pierosandro Tagliaferri
Maria Grazia Cusi
Luciano Mutti
Cirino Botta
Pierpaolo Correale
Source :
Frontiers in Oncology, Vol 12 (2022)
Publication Year :
2022
Publisher :
Frontiers Media S.A., 2022.

Abstract

Peripheral immune-checkpoint blockade with mAbs to programmed cell death receptor-1 (PD-1) (either nivolumab or pembrolizumab) or PD-Ligand-1 (PD-L1) (atezolizumab, durvalumab, or avelumab) alone or in combination with doublet chemotherapy represents an expanding treatment strategy for metastatic non-small cell lung cancer (mNSCLC) patients. This strategy lays on the capability of these mAbs to rescue tumor-specific cytotoxic T lymphocytes (CTLs) inactivated throughout PD-1 binding to PD-L1/2 in the tumor sites. This inhibitory interactive pathway is a physiological mechanism of prevention against dangerous overreactions and autoimmunity in case of prolonged and/or repeated CTL response to the same antigen peptides. Therefore, we have carried out a retrospective bioinformatics analysis by single-cell flow cytometry to evaluate if PD-1/PD-L1-blocking mAbs modulate the expression of specific peripheral immune cell subsets, potentially correlated with autoimmunity triggering in 28 mNSCLC patients. We recorded a treatment-related decline in CD4+ T-cell and B-cell subsets and in the neutrophil-to-lymphocyte ratio coupled with an increase in natural killer T (NKT), CD8+PD1+ T cells, and eosinophils. Treatment-related increase in autoantibodies [mainly antinuclear antibodies (ANAs) and extractable nuclear antigen (ENA) antibodies] as well as the frequency of immune-related adverse events were associated with the deregulation of specific immune subpopulations (e.g., NKT cells). Correlative biological/clinical studies with deep immune monitoring are badly needed for a better characterization of the effects produced by PD-1/PD-L1 immune-checkpoint blockade.

Details

Language :
English
ISSN :
2234943X
Volume :
12
Database :
Directory of Open Access Journals
Journal :
Frontiers in Oncology
Publication Type :
Academic Journal
Accession number :
edsdoj.7c83e17e42a94c91add14fbda6384ccb
Document Type :
article
Full Text :
https://doi.org/10.3389/fonc.2022.911579