Abstract 3451: Single-cell transcriptomic insights into tumor and immune dynamics driving resistance to ixazomib combined with gemcitabine and doxorubicin in SMARCB1-deficient renal medullary carcinoma
Integrative analysis reveals tumor-immune interactions influencing drug resistance in renal medullary carcinoma, suggesting targeted therapies.
Key Points
The study aims to understand the molecular mechanisms behind resistance to ixazomib combined with gemcitabine and doxorubicin in SMARCB1-deficient renal medullary carcinoma.
Performed single-cell and bulk multi-omic profiling of tumor samples from patients with RMC.
Analyzed 33,410 single cells from 11 patients for cellular heterogeneity and immune microenvironment characteristics.
Conducted copy-number and transcriptional state analyses to determine cell responses and resistance mechanisms.
Identified immune-inflamed microenvironments in responding tumors rich in CD8+ T cells and dendritic cells.
Found non-responders exhibited immunosuppressive stromal-myeloid circuits with abundant macrophages and regulatory T cells.
Detected focal gains in genes associated with apoptosis evasion and proteotoxic resilience in non-responders.