The immunopeptidomic landscape of ovarian carcinomas

Abstract

SignificanceDespite the revolution in cancer therapy initiated by checkpoint inhibitors, durable clinical responses remain sporadic in many types of cancer, including ovarian cancer. Understanding which antigens are essentially presented by tumor cells and further able to be recognized by T cells provides a major step toward novel effective targeted immunotherapies. In this study, we comprehensively analyzed the immunopeptidomic landscape of ovarian carcinoma and compared it to variety of benign sources to identify antigens exclusively presented on tumor cells. With personalized therapies moving into the focus of clinical cancer therapy, we further present insights on how gene-expression analysis and immunohistochemistry can support antigen selection for individualized immunotherapy.

Mapping the tumour human leukocyte antigen (HLA) ligandome by mass spectrometry

“…Nevertheless, the isolation of high amounts of both HLA class I‐ and II‐associated peptides from so far all investigated tumour entities does also plead for unimpaired HLA expression on human tumours . Fractionated HLA class I IP of cell populations from enzymatically dissociated EOC with high peptide yields from EpCAM + CD45 − tumour cells further underscores this statement …”

“…HLA ligands have often been isolated from bulk tumour tissue . A more sophisticated approach has been proposed by Schuster et al .…”

“…HLA class II expression on human malignancies such as RCC, colorectal and urothelial carcinoma was substantiated by immunohistochemistry and oligonucleotide microarray . In epithelial ovarian cancer (EOC), both RNA and protein level indicated significantly increased HLA class I and II expression, assigned to EpCAM + CD45 − cancer cells, on tumours versus benign fallopian tubes or ovaries . Surface HLA expression of most haematological malignancies can be easily determined by flow cytometry .…”

“…So far, in‐depth investigations of the non‐mutated immunopeptidome presented on native clinical samples have been published for AML, CLL, MM, mantle cell lymphoma (MCL), EOC, glioblastoma (GBM), and metastatic malignant melanoma (MMM) . From six of these cancer entities both HLA class I and II data have been acquired and analysed (Fig.…”

Minimal Information About an Immuno‐Peptidomics Experiment (MIAIPE)

“…In fact, MS/MS spectrum generation and acquisition is even more important in immunopeptidomics as compared to other sample types due to the very diverse physical chemical properties of these endogenous peptides 25. Thanks to tremendous technological development in the MS/MS field over the last decade, large‐scale MHC‐class I and MHC‐class II immunopeptidome analyses have taken off in recent years,6, 26, 27 thus drastically increasing the availability of immunopeptidome datasets.…”