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Published on: September 25, 2018
PD-1, PD-L1 and PD-L2 Expression in Mantle Cell Lymphoma and Healthy Population
J Karolova1,2, M Radek2,3, K Helman4
1Institute of Pathological Physiology, First Faculty of Medicine, Charles University, Prague, Czech Republic.
Insights
Immune checkpoint PD-1, PD-L1, and PD-L2 expression is low on mantle cell lymphoma cells. Age-dependent increases in these checkpoints were noted in healthy individuals, suggesting they are not effective therapeutic targets for MCL.
Area of Science:
- Immunology
- Oncology
- Flow Cytometry
Background:
- Immune checkpoint expression on mantle cell lymphoma (MCL) cells is poorly understood.
- Ambiguous findings hinder the use of immune checkpoint inhibitors (ICIs) in MCL therapy.
Purpose of the Study:
- To investigate the surface expression of PD-1, PD-L1, and PD-L2 on B and T cells in MCL patients.
- To compare expression levels with chronic lymphocytic leukemia (CLL) and healthy controls.
- To explore age-dependent changes in immune checkpoint expression in healthy individuals.
Main Methods:
- Multiparameter flow cytometry was used to analyze PD-1, PD-L1, and PD-L2 expression.
- Samples were obtained from 31 newly diagnosed MCL patients, 26 newly diagnosed CLL patients, and 20 healthy volunteers.
- A subanalysis of 30 healthy volunteers (ages 25-93) examined age-related expression changes.
Main Results:
- Mantle cell lymphoma patients exhibited weak (<10%) surface expression of PD-1, PD-L1, and PD-L2 on B and T cells compared to healthy individuals.
- Healthy volunteers showed a significant age-dependent increase in PD-1 and PD-L2 expression.
- Chronic lymphocytic leukemia data was also collected for comparison.
Conclusions:
- PD-1 and its ligands (PD-L1, PD-L2) are unlikely to be effective therapeutic targets in mantle cell lymphoma.
- Age-related changes in immune checkpoint expression in the healthy population may influence ICI efficacy and cancer incidence.
- Further research is needed to understand the clinical implications of these age-dependent changes.
Abstract:
Cell surface expression of PD-1, PD-L1 and PD-L2 immune checkpoints on B and T cells obtained from patients with mantle cell lymphoma shows ambiguous results across many studies and creates obstacles for the implementation of immune checkpoint inhibitors into the therapy of mantle cell lymphoma. Using multiparameter flow cytometry we analysed surface expression of PD-1, PD-L1 and PD-L2 molecules on B and T cells of 31 newly diagnosed mantle cell lymphomas and compared it with the results of 26 newly diagnosed chronic lymphocytic leukaemias and 20 healthy volunteers. To gain insight into the age-dependent changes of surface expression of these immune checkpoints, flow cytometric subanalysis of 30 healthy volunteers of 25-93 years of age was conducted. Overall, we demonstrated weak surface expression of PD-1, PD-L1 and PD-L2 on B and T cells of mantle cell lymphoma patients (< 10 % when compared to healthy individuals). A significant age-dependent increase in the expression of PD-1 and its ligand PD-L2 was observed in healthy volunteers. Our results suggest that neither PD-1 nor its ligands represent relevant druggable targets for the therapy of mantle cell lymphoma. The observed age-dependent changes in healthy population could impact efficiency of immune checkpoint inhibitors and could be at least partly connected with increased incidence of cancer with age.
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