Single-cell transcriptome sequencing coupled with a cell-free DNA methylation panel to examine immunotherapy response in metastatic soft tissue sarcoma

Soft tissue sarcoma (STS) represents the second most common solid cancer in children. Almost 50% of STS patients develop metastatic disease and the median overall survival is only 12-18 months. Immunotherapy (IO) has seen great success in the treatment of various cancers and recent evidence suggests that a subgroup of STS may be sensitive to IO. However, we have no means of identifying STS patients who will respond to IO.
Blood biopsies are minimally invasive, enabling routine collection for longitudinal disease monitoring. Biological markers such as circulating peripheral blood mononuclear cells (PBMCs) and DNA have been detected in blood biopsies, and these have shown prognostic and predictive value in certain cancers.
This study will be conducted on a rare and unique cohort of STS patients treated with IO (n=20) with matched clinical and multiomics data. Single-cell RNA sequencing (scRNA-seq) of longitudinal PBMCs will be performed to examine underlying mechanisms of IO response. We will also develop a novel assay based on the circulating DNA methylation profile of STS patients to differentiate IO responders and non-responders. These outcomes can provide a means to select STS patients to improve IO response, and to prescribe alternate trial therapies for non-responding patients.