The effect of anti-PD1 and anti-PDL1 on the cytokine profile and immune system

Overview

Programmed cell death -1 (PD-1) is an inhibitory receptor expressed on a variety of immune cells that provides a checkpoint against autoimmunity. The binding of PD-1 to its ligand, PD-L1, inhibits T cell function, proliferation, and cytokine production, and promotes apoptosis. Some cancer cells express high levels of PD-L1 and use this mechanism to evade attack. Immune checkpoint inhibitors, anti-PD1 and anti-PDL1, block this binding and allow Tcells to attack cancer cells. However, these treatments have varying efficacy and more than 27% of patients experience adverse effects (Gong et al., 2018). This indicates that anti-PD1 and anti-PDL1 alter the healthy immune system. The goal of this study was to examine the effects of anti-PD1 and anti-PDL1 on the cytokine profile and immune system composition of healthy wild type mice to identify possible biomarkers for an adverse reaction to treatment. The cytokine profile of the serum and the immune landscape of the spleen of the mice treated with either anti-PD1, antiPDL1, or a control isotype were examined. These studies indicated that among the several cytokines tested, B Lymphocyte Chemoattractant (BLC), a chemotactic cytokine for Bcells, and TIMP Metallopeptidase Inhibitor 1(TIMP-1), a signaling molecule that influences cell growth, apoptosis, and differentiation, were upregulated following anti-PD1 treatment. Additionally, immunophenotyping studies indicated that Bcells and CD4+ and CD8+ Treg cells were up-regulated by treatment with both anti-PD1 and anti- PDL1. The adverse effects and varying efficacy of anti-PD1 and anti-PDL1 may be linked to these changes in the healthy immune system. Reference List: Gong, Jun, et al. “Development of PD-1 and PD-L1 Inhibitors as a Form of Cancer Immunotherapy: a Comprehensive Review of Registration Trials and Future Considerations.” Journal for Immunotherapy of Cancer, BioMed Central, 23 Jan. 2018. Accessed on June 5, 2019.

Competition history

• JSHS 2020 Category not listed

Resources

• National JSHS abstract book ↗

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