Tuesday, October 22, 2024 1pm to 2pm
About this Event
25 Park Place, Atlanta, GA
Date and Time: 10/22/2024, 13:00--14:00
Location: 25 Park Place, Room 1422
Applied and Computational Math Seminar: Immunogenic cell death: the key to unlocking the potential of combined immuno- and radiation therapy in cancer
Speaker: Somiya Rauf, Department of mathematics & Statistics, GSU
Title: Immunogenic cell death: the key to unlocking the potential of combined immuno- and radiation therapy in cancer
Abstract: In cancer treatment, immunogenic cell death (ICD) triggered by irradiation or chemotherapy promotes the release of tumor-associated antigens, changes the tumor microenvironment, and activates the anti-tumor immune system response. Here, we develop a mathematical model to determine the role of ICD in combined, macrophage-based immunotherapy and radiotherapy, focusing on the SIRPα-CD47 pathway. The model is calibrated using tumor growth in preclinical murine models of SIRPα perturbation, with and without local irradiation. The model first dis- covers that radiotherapy invokes minimal ICD in tumors in wild-type mice, and that ICD depends on radiation dose and tumor size in SIRPα-deficient mice. ICD levels are highest in SIRPα-deficient mice, followed by injection of SIRPα-deficient macrophages in wild-type mice, then treatments of anti-SIRPα, anti-CD47, and finally CD47 knockout. The control group shows the lowest ICD. Analysis of the phagocytosis parameter reveals that SIRPα-deficient mice exhibit the highest phagocytic activity, resembling M1 phenotype, followed by CD47-knockout and SIRPα-deficient macrophage injections, anti-SIRPα, anti-CD47, while wild-type macrophages show no phagocytosis activity, indicative of an M2-like phenotype. Moreover, the model predicts the abscopal effect of the combined radio- and macrophage-based immuno- therapy. Using this calibrated model, we predict the treatment efficacy given radiation doses, macrophage phagocytosis capacity, and ICD strength, for various tumor sizes. The results highlight the critical role of ICD in capitulating the efficacy of the combined radio- and immuno-therapies and offer a new framework to better conceptualize and design optimal cancer treatment strategies.
Host: Pejman Sanaei (psanaei@gsu.edu)
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