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Identification of major histocompatibility complex class I ligands in ovarian adenocarcinoma tumors

ABSTRACT: BACKGROUND. For developing targeted immunotherapy against ovarian adenocarcinoma, direct identification of peptides presented by major histocompatibility complex class I (HLA I) on the surface of tumor cells can be utilized.AIM. To identify ligands of HLA I of ovarian adenocarcinoma tumors. METHODS. Immunopeptidome from postoperative material of patients with ovarian adenocarcinoma were isolated using immunoaffinity chromatography and analyzed by liquid chromatography-mass spectrometry.RESULTS. Using NP-40, 5 peptides belonging to the proteins of cancer/testis antigens (CTA) were identified in the immunopeptidomes of postoperative material from patients with ovarian adenocarcinoma, 3 of which, according to the human protein atlas, are indeed not expressed in normal ovarian tissues.CONCLUSION. Immunopeptidome analysis allows the identification of peptides of CTA proteins, but a larger sample of postoperative material from patients with ovarian adenocarcinoma and experimental testing of the immunogenicity of the identified peptides are needed for further research.

INSTRUMENT(S):

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Ovary, Malignant Cell

DISEASE(S): Malignant Neoplasm Of Ovary

SUBMITTER: Georgij Arapidi

LAB HEAD: Georgij Arapidi

PROVIDER: PXD077095 | Pride | 2026-04-15

REPOSITORIES: Pride

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Project description:The fallopian tube epithelium is one of the potential sources of high-grade serous ovarian cancer (HGSC). The use of estrogen only hormone replacement therapy increases ovarian cancer risk. Despite estrogenâ??s influence in OVCA, selective estrogen receptor modulators (SERMs) typically demonstrate only a 20% response rate. This low response could be due to a variety of factors including the loss of estrogen receptor signaling or the role of estrogen receptor signaling in different potential cell types of origin. The response of fallopian tube epithelium to SERMs is not known, and would be useful when determining therapeutic options for tumors that arise from this cell type, such as high-grade serous cancer. Using normal murine derived oviductal epithelial cells (mouse equivalent to the fallopian tube) estrogen receptor expression was confirmed and interaction with its ligand, estradiol, triggered mRNA and protein induction of progesterone receptor (PR). The SERMs 4-hydroxytamoxifen, raloxifene and desmethylarzoxifene, functioned as estrogen receptor antagonists in the oviductal cells. Cellular proliferation and migration assays suggested that estradiol does not significantly impact cellular migration and increased proliferation in CD1, but not in FVB derived cell lines. Further, using RNAseq, the oviduct specific transcriptional genes targets of estrogen and 4-hydroxytamoxifen signaling were determined and validated. The RNA-seq revealed enrichment in proliferation, anti-apoptosis, calcium signaling and steroid signaling processes. Finally, the ER and PR receptor status of a panel of HGSC cell lines was investigated highlighting the need for better models of estrogen responsive HGSC cell lines. Murine oviductal epithelial cells from the FVB background were hormone starved for 48 hours (with a media change after 24 hours), then treated in triplicate with solvent control (DMSO) (0.1%), 1 nM 17-betaestradiol or 100 nM 4-hydroxytamoxifen for 24 hours. Following treatment, RNA was was isolated, libraries were prepped and sequenced using the Illumina HiSeq 2500 platform.

			Action	DRS
	P1027.dat	Other
	P1027.mgf	Mgf
	P1027.mzid	Mzid
	P1027.mzid_P1027.MGF	Mzid
	P1027.raw	Raw

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Identification of major histocompatibility complex class I ligands in ovarian adenocarcinoma tumors

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