Tumor gene expression analysis of synovial sarcoma patients treated with NY-ESO-1 TCR T cells (NCT01343043) [Immune]

Autologous T cells transduced to express a high affinity T-cell receptor specific to NY-ESO-1 (letetresgene autoleucel, lete-cel) show promise in the treatment of metastatic synovial sarcoma, with 50% overall response rate. Biomarkers predictive of response and resistance remain to be better defined. In 45 synovial sarcoma patients, we analyzed the association of response to lete-cel (NCT01343043) with tumor gene expression. Analysis of tumor samples post-treatment illustrated lete-cel infiltration and decreased expression of macrophage genes, suggesting remodeling of the tumor microenvironment. This dataset consists of 23 tumor samples collected from synovial sarcoma patients pre or post treatment with NY-ESO-1 TCR T cells in trial NCT01343043. There are 13 pre-infusion samples from 10 patients; 3 patients had two samples tested in replicate, results were averaged for downstream analysis. There are 5 at-progression samples. Five samples were excluded from downstream analysis due to time of collection and focus of analysis (see Sample notes for more details). For each sample, five 4-µm unstained slides were used for macrodissection and subsequent RNA extraction. RNA extract was quantified (including assessment of RNA purity) using the Quant-iT RiboGreen RNA Reagent and Kit, and RNA quality was assessed using Agilent RNA Pico chip analysis. RNA was analyzed using the NanoString nCounter® system, with 2 sets of NanoString assays (nCounter® PanCancer Immune Profiling Panel and nCounter® PanCancer Pathway Panel) run on the same extract. The normalization for raw nCounter counts of expressed genes was separately done for QC-passed samples in PanCancer immune and PanCancer pathway panel using the R-package “NanoStringNorm” (R version 4.0.3) with a set of parameters; CodeCount = ‘geo.mean’, Background = ‘mean.2sd’, SampleContent = ‘housekeeping.geo.mean’, round.values = TRUE, take.log = TRUE. nCounter® PanCancer Immune Profiling Panel *** Submitter declares that individual raw reads are not provided in order to protect patient privacy. ***