Germline genetic polymorphisms influence tumor gene expression and immune cell infiltration
Menée à partir des données du projet "The Cancer Genome Atlas" portant sur 24 types de cancers humains et à l'aide de l'approche méthodologique eQTL, cette étude met en évidence l'influence des polymorphismes génétiques héréditaires sur l'expression des gènes de la tumeur et l'infiltration tumorale des cellules immunitaires
Cancer immunotherapy has emerged as an effective therapy in a variety of cancers. However, a key challenge in the field is that only a subset of patients who receive immunotherapy exhibit durable response. It has been hypothesized that host genetics influences the inherent immune profiles of patients and may underlie their differential response to immunotherapy. Herein, we systematically determined the association of common germline genetic variants with gene expression and immune cell infiltration of the tumor. We identified 64,094 expression quantitative trait loci (eQTLs) that associated with 18,210 genes (eGenes) across 24 human cancers. Overall, eGenes were enriched for their being involved in immune processes, suggesting that expression of immune genes can be shaped by hereditary genetic variants. We identified the endoplasmic reticulum aminopeptidase 2 (ERAP2) gene as a pan-cancer type eGene whose expression levels stratified overall survival in a subset of patients with bladder cancer receiving anti–PD-L1 (atezolizumab) therapy. Finally, we identified 103 gene signature QTLs (gsQTLs) that were associated with predicted immune cell abundance within the tumor microenvironment. Our findings highlight the impact of germline SNPs on cancer-immune phenotypes and response to therapy; and these analyses provide a resource for integration of germline genetics as a component of personalized cancer immunotherapy.