Germline genetic polymorphisms influence tumor gene expression and immune cell infiltration
Yoong Wearn Lim1, Haiyin Chen-Harris1, Oleg Mayba2
1Department of Cancer Immunology, Genentech, South San Francisco, CA 94080.
Summary
Host genetics influences cancer immunotherapy response. This study links common genetic variants to gene expression and immune cell infiltration, identifying ERAP2 as a key gene impacting survival in bladder cancer patients treated with anti-PD-L1 therapy.
Area of Science:
- Genomics
- Immunology
- Oncology
Background:
- Cancer immunotherapy offers effective treatment but benefits only a subset of patients.
- Host genetics may influence individual immune profiles and treatment response.
Purpose of the Study:
- To systematically investigate the association between germline genetic variants and gene expression/immune cell infiltration in tumors.
- To identify genetic factors influencing cancer-immune phenotypes and immunotherapy response.
Main Methods:
- Analysis of expression quantitative trait loci (eQTLs) across 24 human cancers.
- Identification of gene signature quantitative trait loci (gsQTLs) linked to immune cell abundance.
- Evaluation of the endoplasmic reticulum aminopeptidase 2 (ERAP2) gene's association with survival in bladder cancer patients receiving anti-PD-L1 therapy.
Main Results:
- Identified 64,094 eQTLs associated with 18,210 genes (eGenes), enriched for immune processes.
- Discovered ERAP2 as a pan-cancer eGene, with its expression correlating with survival in bladder cancer patients on atezolizumab.
- Found 103 gsQTLs associated with predicted immune cell infiltration within the tumor microenvironment.
Conclusions:
- Germline single nucleotide polymorphisms (SNPs) significantly impact cancer-immune phenotypes and treatment response.
- These findings provide a valuable resource for integrating germline genetics into personalized cancer immunotherapy strategies.
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