Jan Ole Kemnade, MD, Ph.D. from Baylor College of Medicine discusses and ASCO 2020 abstract entitled Computational discovery of non-mutational tumor-restricted antigens reveals evidence of immunoediting in head and neck squamous cell carcinoma
We previously identified 107 tumor antigens (EbTAgs), defined as genes with negligible expression in healthy tissue and cancer overexpression. EbTAgs present novel adaptive anti-tumor immune response targets and display signs of immunoediting in highly immune oral cavity infiltrated tumors. The EbTAgs expression was contrasted between four HNSCC subtypes in the sense of tumor immune infiltration: oral cavity (OC), HPV+ oropharyngeal (HPV+OP), HPV- oropharyngeal (HPV-OP), and laryngeal / hypopharyngeal (LH) to detail the landscape of EbTAgs in head and neck squamous cell carcinoma (HNSC) and further elucidate EbTAg immunoediting.
For all HNSC samples, the upper quartile FPKM gene expression values of all protein coding genes were determined using RNAseq data from The Cancer Genome Atlas ( TCGA). TCGA HNSC tumors have been classified into subtypes and tested for expression of EbTAg. Using unsupervised clustering of 14 immune cell signature ssGSEA scores for the HNSC dataset as a whole and for each subtype, the individual tumor sample immune infiltrate was calculated.
LH tumors, specifically HPV+OP (p=0.0008, Tukey 's test), exhibited substantially more EbTAgs than other subtypes (p=0.0014). Analysis of the immune clustering found that LH tumors were substantially more likely to be in the lower than the large immune cluster while the opposite was true for tumors with HPV+OP (p<0.0001). Hypothesizing that the expression of EbTAg was a function of tumor immune infiltration rather than a subtype of HNSC, we compared the expression of EbTAg between tumors in low and high immune clusters of the entire HNSC dataset and of each HNSC subset. In contrast with high immune tumors in the HNSC dataset, substantially more EbTAgs were expressed in low immune tumors (p<0.0001). Similarly, substantially more EbTAgs were expressed in low immune tumors relative to high immune tumors in the OC, OP-all tumors, and HPV+OP datasets (p=0.0003, p<0.0001, p=0.0006) with a pattern of more EbTAgs in the HPV-OP and LH datasets (p=0.12, p=0.095) in the immune low versus high tumors.
In TCGA HNSC samples, EbTAg expression correlates with tumor immune infiltration, resulting in lower expression under higher immune strain. These findings support the hypothesis that EbTAgs are immunoedited and are applicable to immunology. Exploration of EbTAgs as antigenic targets of modular or adoptive T-cell therapy vaccines as well as biomarkers of response therapy to immune control point inhibition is warranted.