A Tumor-Immune Interaction Model for Synergistic Combinations of Anti PD-L1 and Ionizing Irradiation Treatment

Abstract

Combination therapy with immune checkpoint blockade and ionizing irradiation therapy (IR) generates a synergistic effect to inhibit tumor growth better than either therapy does alone. We modeled the tumor-immune interactions occurring during combined IT and IR based on the published data from Deng et al. The mathematical model considered programmed cell death protein 1 and programmed death ligand 1, to quantify data fitting and global sensitivity of critical parameters. Fitting of data from control, IR and IT samples was conducted to verify the synergistic effect of a combination therapy consisting of IR and IT. Our approach using the model showed that an increase in the expression level of PD-1 and PD-L1 was proportional to tumor growth before therapy, but not after initiating therapy. The high expression level of PD-L1 in T cells may inhibit IT efficacy. After combination therapy begins, the tumor size was also influenced by the ratio of PD-1 to PD-L1. These results highlight that the ratio of PD-1 to PD-L1 in T cells could be considered in combination therapy.

Mathematical modeling of radiotherapy and its impact on tumor interactions with the immune system

“…Byun et al. investigated the relationship between the ratio of PD-1 and PD-L1 expression levels and the tumor size pre- and post-treatment with radio-immunotherapy [121] . The efficacy of both treatments is modelled by exponential decay.…”

Modeling Radioimmune Response—Current Status and Perspectives

“…The model of Byun et al. ( 25 ) provides an explicit simulation of both the PD-1 and the PD-L1 concentration, which mainly determine the interaction between tumor cells and T cells. They assume a decaying action strength of both radiation and administered drugs, and consider the binding kinetics of immune checkpoints, modified by checkpoint blocking antibodies.…”

An in silico model to study the impact of carbonic anhydrase IX expression on tumour growth and anti-PD-1 therapy

“…Lai et al [17] built and analysed a continuous model of anti-PD-1 coupled with anti-TNF-α therapy. Byun et al [18] used a compartmental model to study the synergistic combination of anti-PD-1 and radiotherapy. However, the intricacies of the influence of the tumour microenvironment (TME) on the success of ICI therapy are still underexplored [19,20].…”