A catalog of HLA type, HLA expression, and neo-epitope candidates in human cancer cell lines

Abstract

Cancer cell lines are a tremendous resource for cancer biology and therapy development. These multipurpose tools are commonly used to examine the genetic origin of cancers, to identify potential novel tumor targets, such as tumor antigens for vaccine devel­opment, and utilized to screen potential therapies in preclinical studies. Mutations, gene expression, and drug sensitivity have been determined for many cell lines using next-generation sequencing (NGS). However, the human leukocyte antigen (HLA) type and HLA expression of tumor cell lines, characterizations necessary for the development of cancer vaccines, have remained largely incomplete and, such information, when available, has been distributed in many publications. Here, we determine the 4-digit HLA type and HLA expression of 167 cancer and 10 non-cancer cell lines from publically available RNA-Seq data. We use standard NGS RNA-Seq short reads from “whole transcriptome” sequencing, map reads to known HLA types, and statistically determine HLA type, heterozygosity, and expression. First, we present previously unreported HLA Class I and II genotypes. Second, we determine HLA expression levels in each cancer cell line, providing insights into HLA downregulation and loss in cancer. Third, using these results, we provide a fundamental cell line “barcode” to track samples and prevent sample annotation swaps and contamination. Fourth, we integrate the cancer cell-line specific HLA types and HLA expression with available cell-line specific mutation information and existing HLA binding prediction algorithms to make a catalog of predicted antigenic mutations in each cell line. The compilation of our results are a fundamental resource for all researchers selecting specific cancer cell lines based on the HLA type and HLA expression, as well as for the development of immunotherapeutic tools for novel cancer treatment modalities.

MHC class I loaded ligands from breast cancer cell lines: A potential HLA-I-typed antigen collection

“…Our HLA typing agrees with the data published by Boegel et al [29]; however, there is a discrepancy between our data and the data used by the TRON Cell Line Portal (http://celllines.tron-mainz.de/) with regard to MCF-7 cell line. This discrepancy could arise if there were multiple, genetically unique subpopulations within the MCF-7 breast cancer cell line as described by Tan et al [42].…”

“…We identified MHC class I alleles in the breast cancer cell lines by RNA-seq using seq2HLA [33] to map RNA-seq reads against a reference database of HLA alleles [29] (Table 1). Our HLA typing agrees with the data published by Boegel et al [29]; however, there is a discrepancy between our data and the data used by the TRON Cell Line Portal (http://celllines.tron-mainz.de/) with regard to MCF-7 cell line.…”

“…For the identification of recently predicted mutation-containing HLA peptides [29], the Thermo LTQ RAW files were converted to compressed text files using MSConvert of the ProteoWizard (version 3.0.11383) toolkit [30]. Comet (version 2017.01 rev.…”

“…Comet (version 2017.01 rev. 2) [31] was used to search a custom FASTA database constructed from predicted HLA peptides [29] to assign peptide spectrum matches (PSMs). The Comet parameters were an average parent ion mass tolerance of 2.5 Da, a monoisotopic fragment ion mass tolerance of 1.0005 Da, no static amino acid modifications, variable oxidation of methionine (M+15.9949 Da), and no enzyme for the protein digestion.…”

“…The Comet parameters were an average parent ion mass tolerance of 2.5 Da, a monoisotopic fragment ion mass tolerance of 1.0005 Da, no static amino acid modifications, variable oxidation of methionine (M+15.9949 Da), and no enzyme for the protein digestion. The FASTA database was created from the peptides listed in Supplemental Table 4 of [29]. The FASTA accession (key) was constructed by concatenating the cell line name, the protein identifier, and the peptide sequence.…”