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=Volume 12 - 2022

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=PD-1/PDL1-immunecheckpoint blockade with mAbs to PD-1 (nivolumab or pembrolizumab) or PDL-1 (atezolizumab, durvalumab, or avelumab) alone or in combination with doublet chemotherapy, represents an expanding treatment strategy for metastatic NSCLC patients. This strategy lays on the capability of these mAbs of rescuing cytotoxic-T-cells inactivated by PD-1 engagement with PD-L1/2 within the tumor along the long lasting cancerogenesis process. This inhibitory interactive pathway is a physiological host mechanism aimed to prevent dangerous over-reactions and autoimmunity in case of prolonged and/or repeated CTL-response to the same antigen peptides. We have carried out a retrospective analysis to evaluate the ability of PD-1/PD-L1 blocking mAbs to trigger autoimmunity in 28 mNSCLC patients and possible changes in specific peripheral immuno-cell subsets, analyzed by flow-cytometry single cell bioinformatic approach. We recorded a treatment-related decline in the CD4+T, B cells and neutrophil to lymphocyte ratio, coupled with an increase of NKT, CD8+PD1+ T and eosinophils. Treatment-related increase in auto-antibodies as well as frequency of immune-related adverse events was also observed, and it was frequently associated with deregulation of specific immune subpopulations (e.g. NKT cells). Correlative biological/clinical studies with deep immune-monitoring are eagerly awaited to better characterize the effects produced by PD-1/PD-L1 immune-checkpoint blockade.