The neoepitope landscape of breast cancer: implications for immunotherapy

Cancer immunotherapy with immune checkpoint blockade (CKB) is now standard of care for multiple cancers. The clinical response to CKB is associated with T cell immunity targeting cancer-induced mutations that generate novel HLA-binding epitopes (neoepitopes). Here, we developed a rapid bioinformatic...

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Bibliographic Details
Published in:BMC cancer 2019-03, Vol.19 (1), p.200-200, Article 200
Main Authors: Narang, Pooja, Chen, Meixuan, Sharma, Amit A, Anderson, Karen S, Wilson, Melissa A
Format: Article
Language:English
Subjects:
Antigenic determinants
Breast cancer
Cancer treatment
Care and treatment
Computational biology
Epitopes
Gene mutation
Genetic aspects
Immunotherapy
Mutation burden
Neoepitope prediction
RNA
T cells
TNBC
Tumors
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Summary:Cancer immunotherapy with immune checkpoint blockade (CKB) is now standard of care for multiple cancers. The clinical response to CKB is associated with T cell immunity targeting cancer-induced mutations that generate novel HLA-binding epitopes (neoepitopes). Here, we developed a rapid bioinformatics pipeline and filtering strategy, EpitopeHunter, to identify and prioritize clinically relevant neoepitopes from the landscape of somatic mutations. We used the pipeline to determine the frequency of neoepitopes from the TCGA dataset of invasive breast cancers. We predicted HLA class I-binding neoepitopes for 870 breast cancer samples and filtered the neoepitopes based on tumor transcript abundance. We found that the total mutational burden (TMB) was highest for triple-negative breast cancer, TNBC, (median = 63 mutations, range: 2-765); followed by HER-2(+) (median = 39 mutations, range: 1-1206); and lowest for ER/PR(+)HER-2(-) (median = 32 mutations, range: 1-2860). 40% of the nonsynonymous mutations led to the generation of predicted neoepitopes. The neoepitope load (NEL) is highly correlated with the mutational burden (R  = 0.86). Only half (51%) of the predicted neoepitopes are expressed at the RNA level (FPKM≥2), indicating the importance of assessing whether neoepitopes are transcribed. However, of all patients, 93% have at least one expressed predicted neoepitope, indicating that most breast cancer patients have the potential for neo-epitope targeted immunotherapy.
ISSN:1471-2407
1471-2407
DOI:10.1186/s12885-019-5402-1