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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
Fameli, Antonella Nardone, Valerio Azgomi, Mojtaba Shekarkar Bianco, Giovanna Gandolfo, Claudia Oliva, Bianca Maria Monoriti, Marika Saladino, Rita Emilena Falzea, Antonella Romeo, Caterina
Fameli, Antonella
Nardone, Valerio
Azgomi, Mojtaba Shekarkar
Bianco, Giovanna
Gandolfo, Claudia
Oliva, Bianca Maria
Monoriti, Marika
Saladino, Rita Emilena
Falzea, Antonella
Romeo, Caterina
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Journal article
Date
2022-09-14
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Biology
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http://dx.doi.org/10.3389/fonc.2022.911579
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.
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Fameli A, Nardone V, Shekarkar Azgomi M, Bianco G, Gandolfo C, Oliva BM, Monoriti M, Saladino RE, Falzea A, Romeo C, Calandruccio ND, Azzarello D, Giannicola R, Pirtoli L, Giordano A, Tassone P, Tagliaferri P, Cusi MG, Mutti L, Botta C and Correale P (2022) 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. Front. Oncol. 12:911579. doi: 10.3389/fonc.2022.911579
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Frontiers in Oncology, Vol. 12
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