Gene expression profiling signatures for immunophenotyping of tumor microenvironment using HTG EdgeSeq Precision Immuno-Oncology Panel.

Abstract

e14528 Background: Immunotherapy has revolutionized cancer treatment by harnessing the power of the patient’s immune system to fight the disease. While immunotherapies have become increasingly effective, the proportion of patients not responding to immunotherapy ranges between only 20-50%. New breakthroughs in the understanding of the tumor immune biology have led to the development of new, more effective therapies; however, these breakthroughs often hinge on tools that can elucidate the role and abundance of individual components of the patient’s immune system in the tumor microenvironment. Methods: This poster describes the performance of 26 gene enrichment signatures that allow for the measurement of the relative abundance of 23 individual immune and stromal cells in the tumor environment, in addition to providing composite inflammation, stroma and tumor microenvironment scores. These Research Use Only (RUO) signatures are based on gene expression profiling (GEP) data for 1,392 genes implicated in tumor-immune interaction generated using the HTG EdgeSeq Precision Immuno-Oncology Panel (RUO). The signatures were developed and validated using GEP data from 1,073 colorectal, gastric and ovarian cancer formalin-fixed paraffin-embedded (FFPE) tissue specimens. Results: The signature accuracy was independently verified by spiking known numbers of representative immune and stromal cells into an FFPE tissue lysate; the signature outputs were highly correlated to the number of immune and stromal cells present in the sample, with Pearson correlation coefficients ranging from 0.71 to 0.98. In addition, the outputs of some of the signatures were compared to multiple commonly used immunohistochemistry markers of immune cells in 61 non-small-cell lung carcinoma FFPE samples. The results showed a high degree of correlation, with Pearson correlation coefficients of 0.77 and 0.81 for CD4 and CD8, respectively. Conclusions: These immunophenotyping signatures provide a suite of robust tools for the characterization of the tumor microenvironment in order to better understand the tumor immune biology and mechanisms of resistance to immunotherapy. The signature scores can typically be generated from a single section of FFPE tissue using HTG’s extraction-free GEP technology and a fully automated bioinformatic pipeline available in the HTG EdgeSeq Reveal software.

Changes in Gene Expression Patterns in the Tumor Microenvironment of Head and Neck Squamous Cell Carcinoma Under Chemoradiotherapy Depend on Response

“…This supports the observation made here of a downregulation of these two genes in poor responder under therapy. The loss of T cell signatures in patients poorly responding to CRT could be further demonstrated using the Immunephenotyping Signatures, which were developed and tested for the 1392 gene panel and are based on the xCell gene set enrichment algorithm (21,22). According to these signatures, CD4 memory T cells were diminished after CRT in responder.…”

“…For immune signature analysis the software platform HTG REVEAL was used. These signatures were developed using the xCell algorithm and have been validated for the HTG EdgeSeq Precision Immuno-Oncology Panel (21,22). There are 23 signatures for immune or stromal cell types available.…”