Increased ‘selfness’ in the tumor emerges as a possible immune sculpting mechanism: A pan-cancer data analysis of 32 solid tumors in TCGA

Abstract

AbstractTumors pose a unique challenge to the immune system since they straddle the boundary between ‘self’ and ‘non-self’. T-cells recognize tumors that contain ‘non-self’ neo-antigens. They can also recognize tumors that contain aberrantly expressed self-antigens, highlighting the importance of the central tolerance and the tuning of the T-cell repertoire in the thymus. Therefore, the similarity to the thymic expression profiles must have information in it to influence the T-cell repertoire and what self-peptides are recognized. We utilize this principle in a pan-cancer analysis and develop a thymus-like or ‘selfness’ score (TLS) based on the gene-expression similarity to thymi, indicative of recognizability of tumors by T-cells. We show that the TLS is indicative of patient survival in 8 different TCGA cohorts, indicating gene expression modulation to mimic that in thymi as a potential immune sculpting mechanism. Surprisingly, we also see an inverse relationship between TLS and the degree of immune infiltration.