Publication Date
11-10-2023
Description
Effective anti-cancer immune responses require activation of one or more naïve T cells. If the correct naïve T cell encounters its cognate antigen presented by an antigen presenting cell, then the T cell can activate and proliferate. Here, mathematical modeling is used to explore the possibility that immune activation in lymph nodes is a rate-limiting step in anti-cancer immunity and can affect response rates to immune checkpoint therapy. The model provides a mechanistic framework for optimizing cancer immunotherapy and developing testable solutions to unleash anti-tumor immune responses for more patients with cancer. The results show that antigen production rate and trafficking of naïve T cells into the lymph nodes are key parameters and that treatments designed to enhance tumor antigen production can improve immune checkpoint therapies. The model underscores the potential of radiation therapy in augmenting tumor immunogenicity and neoantigen production for improved ICB therapy, while emphasizing the need for careful consideration in cases where antigen levels are already sufficient to avoid compromising the immune response.
Journal
Advanced Science
Issue
202304076
First Page
1
Last Page
10
Department
Biomedical Engineering
Link to Published Version
https://doi.org/10.1002/advs.202304076
DOI
10.1002/advs.202304076
Recommended Citation
Nikmaneshi, M. R., Baish, J. W., Zhou, H., Padera, T. P., Munn, L. L., Transport Barriers Influence the Activation of Anti-Tumor Immunity: A Systems Biology Analysis. Adv. Sci. 2023, 2304076. https://doi.org/10.1002/advs.202304076