Understanding the impact of microbiome modulations on T cell-mediated immunotherapy for metastatic osteosarcoma (mOS)

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Presentation Time: 11:30 AM - 12:45 PM
Poster Board Number: B221
Abstract ID: 5887

Presenting Author:
Michelle Di Palma , Post Doctoral Fellow at Arizona State Univ.

Abstract:

Osteosarcoma is the most common childhood bone malignancy, with a sharp decline in survival rates upon metastasis. We have previously demonstrated that immune checkpoint blockade (ICB) administered to mice inoculated with a K7M2 metastatic osteosarcoma (mOS) cell line resulted in ~50% survival and complete tumor clearance. Unlike inbred lab mice, human patients have diversity in genetic makeup and copious factors, making it difficult to understand what factors impact ICB efficacy. Recent studies have shown ICB's effectiveness can be associated with or reliant on microbiome composition. Additional findings show that antibiotic treatment can significantly reduce CD3+ T cell presence in the lungs of saline-treated mice during respiratory infections compared to untreated groups. These studies could be significant in the design of mOS immunotherapies, as mOS frequently metastasizes to the lungs, and antibiotic treatments are often needed for patients on ICB who are likely to develop nosocomial infections. We found that microbiome dysbiosis can alter ICB efficacy for mOS under certain circumstances and further that mice treated with antibiotics who reach mOS endpoint criteria display splenomegaly while untreated mice who reach endpoint criteria do not, indicating potential alterations on immune cell homing during antibiotic treatment and mOS progression. Here we analyze both the impact of microbiome depletion on ICB efficacy as well as its impact on T immune cell homing during mOS.