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Spatio-Temporal Modeling of TNBC Tumor Microenvironment for Combination Immunotherapy

AJAS · 2025 Computational Biology and Bioinformatics (inferred)

Ajeet Venkatesh · Washington State Academy of Sciences

Overview

Breast cancer affects 2.3 million women annually with the five-year survival rate for triple-negative-breast-cancer (TNBC) around 12%. Current immunotherapy treatments are effective only in 25% patients as the multiple immunosuppressive mechanisms of the tumor-microenvironment (TME) are not well understood. T-STM is the first of its kind multi-agent, spatio-temporal- modeling-based simulation of the TNBC TME. T-STM uses a novel hybrid approach with discrete models to characterize tumor, stromal and immune interactions; driven by tumor and patient-specific metabolic profiles, signaling and immune infiltration patterns derived from TCGA(The-Cancer-Genome-Atlas) data along with partial-differential-equations for modeling nutrient diffusion and the multiple immunosuppressive pathways in the TME. Simulation results were successfully validated with TCGA histopathological immunophenotypes matching and cell fraction histograms showing high correlation with r values (i..e, 0.785 - 0.81). Multiple simulations were run on 100 TNBC datasets for 150 days testing for optimal combinations of immunomodulatory drugs for tumor eradication. The combination of TLR9 agonist with P13k, mTOR and IDO inhibitors combined with LAG3 and PDL1 blockade resulted in the highest tumor remission with an average of 80% reduction in tumor cells across 40 datasets. T-STM showed best immune-efficacy with low stroma and high tumor-infiltrating-lymphocytes scenario validated by Kaplan Meier survival curves and stromal permeability boost increasing immune response. T-STM has a potential to shorten the drug development cycle through identification of combination therapies based on simulated remission rates and create customized therapies for enhanced cancer immunotherapy with reduced costs.

Competition history

  • AJAS 2025 Category not listed

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Source: AAAS Annual Meeting (Confex) / American Junior Academy of Science

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