RT Journal Article
SR Electronic
T1 Multi-scale modeling of macrophage – T cell interactions within the tumor microenvironment and impacts of macrophage-based immunotherapies
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2020.08.03.235333
DO 10.1101/2020.08.03.235333
A1 Cess, Colin G.
A1 Finley, Stacey D.
YR 2020
UL http://biorxiv.org/content/early/2020/08/03/2020.08.03.235333.abstract
AB Within the tumor microenvironment, macrophages exist in an immunosuppressive state, preventing T cells from eliminating the tumor. Due to this, research is focusing on immunotherapies that specifically target macrophages in order to reduce their immunosuppressive capabilities and promote T cell function. In this study, we develop an agent-based model consisting of the interactions between macrophages, T cells, and tumor cells to determine how the immune response changes due to three macrophage-based immunotherapeutic strategies: macrophage depletion, recruitment inhibition, and macrophage reeducation. We find that reeducation, which converts the macrophages into an immune promoting phenotype, is the most effective strategy and that the macrophage recruitment rate and tumor proliferation rate (tumor-specific properties) have large impacts on therapy efficacy. We also employ a novel method of using a neural network to reduce the computational complexity of an intracellular signaling mechanistic model.Competing Interest StatementThe authors have declared no competing interest.