AUTHOR=Fameli Antonella , Nardone Valerio , Shekarkar Azgomi Mojtaba , Bianco Giovanna , Gandolfo Claudia , Oliva Bianca Maria , Monoriti Marika , Saladino Rita Emilena , Falzea Antonella , Romeo Caterina , Calandruccio Natale Daniele , Azzarello Domenico , Giannicola Rocco , Pirtoli Luigi , Giordano Antonio , Tassone Pierfrancesco , Tagliaferri Pierosandro , Cusi Maria Grazia , Mutti Luciano , Botta Cirino , Correale Pierpaolo TITLE=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 JOURNAL=Frontiers in Oncology VOLUME=12 YEAR=2022 URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2022.911579 DOI=10.3389/fonc.2022.911579 ISSN=2234-943X 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.