Conclusions
This study provides a framework for studying rare tumors and identifies salient and treatment-associated cancer cell intrinsic and tumor microenvironmental features in sarcomas.
Purpose
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
Results
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. Conclusions: This study provides a framework for studying rare tumors and identifies salient and treatment-associated cancer cell intrinsic and tumor microenvironmental features in sarcomas.