Abstract 2741: A communication theory framework for modeling cytokine-mediated signaling in healthy and breast cancer derived peripheral blood immune cells

Abstract

Abstract Previous studies have shown that approximately 40% of estrogen receptor positive (ER+) breast cancer (BC) patients harbor immune signaling defects in their blood at diagnosis that predicts overall survival. The aim of this work is to apply communication theory and signal processing methods to model cytokine-mediated signaling errors in immune cells in the peripheral blood. Our approach uses communication theory concepts to develop a communication system model consisting of a transmitter, receiver, and channel, applied to the JAK/STAT signaling pathway and tested using multi-color flow cytometry analysis of peripheral blood mononuclear cells stimulated with IFNγ, IL-2, IL-6, IL-4, IL-10, IL-12, or TGFβ in samples from 2 BC patients and 4 healthy controls. We use our model to estimate the detection error rate when one of the 7 cytokines is being transduced through the JAK/STAT signaling pathway, but its signal is being received on multiple phosphorylated signal transducers and activators of transcription (pSTAT) molecules. In addition, we extend the measured error rate value to an error rate curve by varying the signal-to-noise ratio available to the receiver in our system model. Our results show a trend towards higher detection error rates in immune cells from BC patients as compared to healthy controls, which may indicate altered immune signaling and incorrect cell decisions in these patients. Also, considering different cell subtypes, our results show two orders of magnitude increase in error rate in CD4+ memory T cells compared to CD4+ naïve T cells in BC patients. With further development, we believe that our communication theory model and quantification of optimal signal detection in cells will provide a better understanding into how immune cells can accurately “decode” information to respond properly to various signals and how the immune signaling is altered in BC patients, causing better or worse outcomes. The benefit of our novel approach is that it integrates all the transmitted (cytokines) and received signals (pSTATs) into a single communications framework that can be efficiently analyzed together. Citation Format: Adina Matache, Aleksandra Karolak, Sergio Branciamore, Andrei Rodin, Peter P. Lee, Russell C. Rockne. A communication theory framework for modeling cytokine-mediated signaling in healthy and breast cancer derived peripheral blood immune cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 2741.