Supplementary Figure S1 from Single-Cell Profiling of Sarcomas from Archival Tissue Reveals Programs Associated with Resistance to Immune Checkpoint Blockade

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posted on 2024-10-01, 07:21 authored by Karan 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

Violin plots and boxplots displaying the (a) genes detected per cell and (b) stress signature expression per cell and (c) mitochondrial fraction of reads in samples profiled from fresh or frozen tissue in this study and in indicated studies by Jerby et. al. (dijon) and Slyper et al. (green), respectively. The upper and lower edges of the boxplot display the 75th and 25th percentiles respectively. Blue violin plots are from scRNA-seq from fresh tissue, and red violin plots are from snRNA-seq on frozen tissue.

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.