Changes in Gene Expression Caused by Head and Neck Cancer
What are cancers of the head and neck?
National Cancer Institute explains that “cancers known collectively as head and neck cancers usually begin in the squamous cells that line the mucosal surfaces of the head and neck (for example, those inside the mouth, throat, and voice box). These cancers are referred to as squamous cell carcinomas of the head and neck. Head and neck cancers can also begin in the salivary glands, sinuses, or muscles or nerves in the head and neck, but these types of cancer are much less common than squamous cell carcinomas”.
Doescher et al., researchers from the United Kingdom and Germany, set out to understand the impact of chemoradiotherapy (CRT) on the tumor microenvironment (TME) of head and neck squamous cell carcinoma (HNsqCC) patients. Their goal was to gain a deeper understanding of the results of resent clinical trials, and explain some unexpected failures of past studies (e.g. TME JAVELIN Head and Neck 100 trial) which were likely due to unfavorable changes in the tumor microenvironment. Their resent publication titled “Changes in Gene Expression Patterns in the Tumor Microenvironment of Head and Neck Squamous Cell Carcinoma Under Chemoradiotherapy Depend on Response” published in Frontiers in Oncology describes some interesting findings which are summarized below.
In their study the researchers used HTG EdgeSeq Precision Immuno-Oncology Panel (PIP). The next-generation sequencing (NGS)-based HTG EdgeSeq Precision Immuno-Oncology Panel is designed to measure the immune response both inside the tumor and the surrounding microenvironment. HTG’s quantitative nuclease protection assay does not require nucleic acid extraction and is automated using the HTG EdgeSeq processor. By leveraging the high sensitivity and dynamic range of NGS instrumentation, this powerful tool interrogates 1,392 genes from a single section of formalin-fixed, paraffin-embedded (FFPE) tissue, extracted RNA, or PAXgene samples.
In the study the researches looked at 60 archived HNsqCC FFPE biopsies from 30 patients pre and post 12 weeks CRT treatment. It was found that:
- There was a relevant difference in the number of differentially expressed genes between the total cohort and patients with residual disease.
- Genes involved in T cell activation showed significantly reduced expression in tumors after therapy and gene enrichment for several T cell subsets was also observed.
- Differential gene expression was observed in tumor microenvironments revealed by the combination of single cell research and bulk RNA analysis using the HTG EdgeSeq platform.
- From this study it was not clear that adding anti-PD-1 antibodies alone to CRT can prevent treatment failure, since no upregulation of targets was measurable in the TME.
- It is possible that in some patients TRM are depleted by CRT, despite persistence of antigen, which needs to be further studied to protect these patients from potentially harmful treatment.
Figure 1C : Up- and downregulation of T cell related genes after CRT.
Figure 2B: T cell related genes are downregulated after CRT in patients with RD.
Resources:
The full article and the supplemental materials can be accessed by clicking here.