Study Title: A gut microbiota rheostat forecasts responsiveness to PD-L1 and VEGF blockade in mesothelioma
Nature Communications, August 21, 2024
Key Findings:
Malignant mesothelioma, a rare cancer linked to asbestos exposure, has limited treatment options and poor prognosis. A multi-center phase II clinical trial (MiST4, NCT03654833) evaluated atezolizumab and bevacizumab (AtzBev) in relapsed mesothelioma patients, achieving a 50% disease control rate at 12 weeks with tolerable treatment.
Tumor intrinsic resistance factors including aneuploidy, homologous recombination deficiency (HRD), epithelial-mesenchymal transition, and inflammation were identified. The gut-resident microbial genera correlated positively with treatment response and CD8+ T cell infiltration, while inversely correlated with other resistance factors.
A proposed model suggests intrinsic and extrinsic factors in mesothelioma modify the tumor microenvironment, influencing clinical sensitivity to AtzBev. The gut microbiota represent a potentially modifiable factor that could improve immunotherapy outcomes for this unmet medical need.
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