Document Type

Article

Publication Date

7-26-2019

Keywords

JGM

JAX Source

Sci Rep 2019 Jul 26; 9(2):10862

Volume

9

Issue

1

First Page

10862

Last Page

10862

ISSN

2045-2322

PMID

31350431

DOI

https://doi.org/10.1038/s41598-019-47333-y

Grant

CA034196

Abstract

Combined agonist stimulation of the TNFR costimulatory receptors 4-1BB (CD137) and OX40(CD134) has been shown to generate supereffector CD8 T cells that clonally expand to greater levels, survive longer, and produce a greater quantity of cytokines compared to T cells stimulated with an agonist of either costimulatory receptor individually. In order to understand the mechanisms for this effect, we have created a mathematical model for the activation of the CD8 T cell intracellular signaling network by mono- or dual-costimulation. We show that supereffector status is generated via downstream interacting pathways that are activated upon engagement of both receptors, and in silico simulations of the model are supported by published experimental results. The model can thus be used to identify critical molecular targets of T cell dual-costimulation in the context of cancer immunotherapy.

Comments

This open access article is licensed under a Creative Commons Attribution 4.0 International License

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