Dataset Information

Highly Multiplexed Digital Spatial Profiling of the Tumor Microenvironment of Head and Neck Squamous Cell Carcinoma Patients.

ABSTRACT:

Background

Immune checkpoint inhibitors (ICI) have shown durable and long-term benefits in a subset of head and neck squamous cell carcinoma (HNSCC) patients. To identify patient-responders from non-responders, biomarkers are needed which are predictive of outcome to ICI therapy. Cues in the tumor microenvironment (TME) have been informative in understanding the tumor-immune contexture.

Methods

In this preliminary study, the NanoString GeoMx™ Digital Spatial Profiling (DSP) technology was used to determine the immune marker and compartment specific measurements in a cohort of HNSCC tumors from patients receiving ICI therapy.

Results

Our data revealed that markers involved with immune cell infiltration (CD8 T-cells) were not predictive of outcome to ICI therapy. Rather, a number of immune cell types and protein markers (CD4, CD68, CD45, CD44, CD66b) were found to correlate with progressive disease. Cross platform comparison with the Opal Vectra (Perkin Elmer) for a number of markers across similar regions of interest demonstrated concordance for pan-cytokeratin, CD8, and PD-L1.

Conclusion

This study, to our knowledge, represents the first digital spatial analysis of HNSCC tumors. A larger cohort of HNSCC will be required to orthogonally validate the findings.

SUBMITTER: Kulasinghe A

PROVIDER: S-EPMC7851078 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Publications

Highly Multiplexed Digital Spatial Profiling of the Tumor Microenvironment of Head and Neck Squamous Cell Carcinoma Patients.

Kulasinghe Arutha A Taheri Touraj T O'Byrne Ken K Hughes Brett G M BGM Kenny Liz L Punyadeera Chamindie C

Frontiers in oncology 20210119

<h4>Background</h4>Immune checkpoint inhibitors (ICI) have shown durable and long-term benefits in a subset of head and neck squamous cell carcinoma (HNSCC) patients. To identify patient-responders from non-responders, biomarkers are needed which are predictive of outcome to ICI therapy. Cues in the tumor microenvironment (TME) have been informative in understanding the tumor-immune contexture.<h4>Methods</h4>In this preliminary study, the NanoString GeoMx™ Digital Spatial Profiling (DSP) techno ...[more]

PMID: 33542903

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Project description:Immune checkpoint inhibitors of programmed cell death protein 1 (PD-1) represent a significant breakthrough in treating head and neck squamous cell carcinoma (HNSCC), with long-lasting responses and prolonged survival observed in first- and second-line therapy. However, this is observed in < 20% of patients and high primary/secondary resistance may occur. The primary objective of the identification of predictive factors for the response to anti-PD-1 immunotherapy in head and neck squamous cell carcinoma (IPRICE) study is to identify predictive factors of response to anti-PD-1 immunotherapy. The IPRICE study is a single-center, prospective, non-randomized, open-label, and interventional clinical trial. Liquid and tumor biopsies will be performed in 54 patients with recurrent/metastatic (R/M) HNSCC undergoing anti-PD-1 immunotherapy alone to compare the evolution of gene expression and immunological profile between responders and non-responders. We will use a multidisciplinary approach including spatial transcriptomics, single seq-RNA analysis, clinical data, and medical images. Genes, pathways, and transcription factors potentially involved in the immune response will also be analyzed, including genes involved in the interferon-gamma (IFN-γ) pathway, immunogenic cell death and mitophagy, hypoxia, circulating miRNA-mediated immunomodulation, cytokines, and immune repertoire within the tumor microenvironment (TME). With a follow-up period of 3-years, these data will help generate effective biomarkers to define optimal therapeutic strategy and new immunomodulatory agents based on a better understanding of primary/secondary resistance mechanisms. Tumor biopsy will be performed initially before the start of immunotherapy at the first tumor assessment and is only proposed at tumor progression. Clinical data will be collected using a dedicated Case Report Form (CRF). Identifying predictive factors of the response to anti-PD-1 immunotherapy and optimizing long-term immune response require a thorough understanding of the intrinsic and acquired resistance to immunotherapy. To achieve this, dynamic profiling of TME during anti-PD-1 immunotherapy based on analysis of tumor biopsy samples is critical. This will be accomplished through the anatomical localization of HNSCC, which will allow for the analysis of multiple biopsies during treatment and the emergence of breakthrough technologies including single-cell RNA sequencing (scRNA-seq) and spatial transcriptomics. Clinicaltrial.gov. Registered April 14, 2022, https://www. gov/study/NCT05328024 .

Dataset Information

Highly Multiplexed Digital Spatial Profiling of the Tumor Microenvironment of Head and Neck Squamous Cell Carcinoma Patients.

Background

Methods

Results

Conclusion

Publications

Highly Multiplexed Digital Spatial Profiling of the Tumor Microenvironment of Head and Neck Squamous Cell Carcinoma Patients.

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