Supplementary Table S1 from Single-Cell Profiling of Sarcomas from Archival Tissue Reveals Programs Associated with Resistance to Immune Checkpoint Blockade
posted on 2024-10-01, 07:21authored byKaran Luthria, Parin Shah, Blake Caldwell, Johannes C. Melms, Sinan Abuzaid, Viktoria Jakubikova, D. Zack Brodtman, Sminu Bose, Amit Dipak Amin, Patricia Ho, Jana Biermann, Somnath Tagore, Matthew Ingham, Gary K. Schwartz, Benjamin Izar
Supplemental Table 1: Assays performed and basic quality metrics of included samples.
Funding
Jed Ian Taxel Foundation for Rare Cancer Research
History
ARTICLE ABSTRACT
Sarcoma encompasses a diverse group of cancers that are typically resistant to current therapies, including immune checkpoint blockade (ICB), and underlying mechanisms are poorly understood. The contexture of sarcomas limits generation of high-quality data using cutting-edge molecular profiling methods, such as single-cell RNA-sequencing, thus hampering progress in understanding these understudied cancers.
Here, we demonstrate feasibility of producing multimodal single-cell genomics and whole-genome sequencing data from frozen tissues, profiling 75,716 cell transcriptomes of five undifferentiated pleomorphic sarcoma and three intimal sarcoma samples, including paired specimens from two patients treated with ICB.
We find that genomic diversity decreases in patients with response to ICB, and, in unbiased analyses, identify cancer cell programs associated with therapy resistance. Although interactions of tumor-infiltrating T lymphocytes within the tumor ecosystem increase in ICB responders, clonal expansion of CD8+ T cells alone was insufficient to predict drug responses.
This study provides a framework for studying rare tumors and identifies salient and treatment-associated cancer cell intrinsic and tumor microenvironmental features in sarcomas.