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非突变卵巢癌特异性抗原的免疫原性。

Immunogenicity of Non-Mutated Ovarian Cancer-Specific Antigens.

机构信息

Institute for Research in Immunology and Cancer (IRIC), University of Montreal, Montreal, QC H3T 1J4, Canada.

Department of Chemistry, University of Montreal, Montreal, QC H2V 0B3, Canada.

出版信息

Curr Oncol. 2024 May 30;31(6):3099-3121. doi: 10.3390/curroncol31060236.


DOI:10.3390/curroncol31060236
PMID:38920720
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11203340/
Abstract

Epithelial ovarian cancer (EOC) has not significantly benefited from advances in immunotherapy, mainly because of the lack of well-defined actionable antigen targets. Using proteogenomic analyses of primary EOC tumors, we previously identified 91 aberrantly expressed tumor-specific antigens (TSAs) originating from unmutated genomic sequences. Most of these TSAs derive from non-exonic regions, and their expression results from cancer-specific epigenetic changes. The present study aimed to evaluate the immunogenicity of 48 TSAs selected according to two criteria: presentation by highly prevalent HLA allotypes and expression in a significant fraction of EOC tumors. Using targeted mass spectrometry analyses, we found that pulsing with synthetic TSA peptides leads to a high-level presentation on dendritic cells. TSA abundance correlated with the predicted binding affinity to the HLA allotype. We stimulated naïve CD8 T cells from healthy blood donors with TSA-pulsed dendritic cells and assessed their expansion with two assays: MHC-peptide tetramer staining and TCR Vβ CDR3 sequencing. We report that these TSAs can expand sizeable populations of CD8 T cells and, therefore, represent attractive targets for EOC immunotherapy.

摘要

上皮性卵巢癌 (EOC) 并未从免疫疗法的进步中显著获益,主要是因为缺乏明确的可操作性抗原靶点。我们之前通过对原发性 EOC 肿瘤的蛋白质基因组分析,鉴定出 91 种源自未突变基因组序列的异常表达的肿瘤特异性抗原 (TSA)。这些 TSA 大多数来自非外显子区域,其表达是由于癌症特异性的表观遗传变化。本研究旨在评估根据两个标准选择的 48 种 TSA 的免疫原性:高流行的 HLA 同种型的呈递和在大量 EOC 肿瘤中的表达。使用靶向质谱分析,我们发现合成 TSA 肽脉冲导致树突状细胞高水平呈递。TSA 丰度与预测与 HLA 同种型的结合亲和力相关。我们用 TSA 脉冲树突状细胞刺激来自健康献血者的幼稚 CD8 T 细胞,并通过两种测定法评估其扩增:MHC-肽四聚体染色和 TCR Vβ CDR3 测序。我们报告这些 TSA 可以扩增相当数量的 CD8 T 细胞,因此是 EOC 免疫治疗的有吸引力的靶标。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e263/11203340/62b35172b19d/curroncol-31-00236-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e263/11203340/b4d1c2702e39/curroncol-31-00236-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e263/11203340/7ad34ea92aa0/curroncol-31-00236-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e263/11203340/cda49455f9b1/curroncol-31-00236-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e263/11203340/62b35172b19d/curroncol-31-00236-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e263/11203340/b4d1c2702e39/curroncol-31-00236-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e263/11203340/7ad34ea92aa0/curroncol-31-00236-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e263/11203340/cda49455f9b1/curroncol-31-00236-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e263/11203340/62b35172b19d/curroncol-31-00236-g004.jpg

相似文献

[1]
Immunogenicity of Non-Mutated Ovarian Cancer-Specific Antigens.

Curr Oncol. 2024-5-30

[2]
Proteogenomics Uncovers a Vast Repertoire of Shared Tumor-Specific Antigens in Ovarian Cancer.

Cancer Immunol Res. 2020-2-11

[3]
Monoclonal antibodies targeted against melanoma and ovarian tumors enhance dendritic cell-mediated cross-presentation of tumor-associated antigens and efficiently cross-prime CD8+ T cells.

J Immunother. 2006

[4]
Definition of an immunogenic region within the ovarian tumor antigen stratum corneum chymotryptic enzyme.

Clin Cancer Res. 2005-5-1

[5]
In vitro induction of tumor-specific human lymphocyte antigen class I-restricted CD8 cytotoxic T lymphocytes by ovarian tumor antigen-pulsed autologous dendritic cells from patients with advanced ovarian cancer.

Am J Obstet Gynecol. 2000-9

[6]
Efficient identification of neoantigen-specific T-cell responses in advanced human ovarian cancer.

J Immunother Cancer. 2019-6-20

[7]
Breast cancer immunopeptidomes contain numerous shared tumor antigens.

J Clin Invest. 2024-1-2

[8]
Atypical acute myeloid leukemia-specific transcripts generate shared and immunogenic MHC class-I-associated epitopes.

Immunity. 2021-4-13

[9]
Anti-cancer immune effect of human colorectal cancer neoantigen peptide based on MHC class I molecular affinity screening.

Front Immunol. 2024

[10]
[Identification of T cell epitopes from ovarian cancer associated anti-idiotype antibody].

Zhonghua Fu Chan Ke Za Zhi. 2008-10

引用本文的文献

[1]
Tumor antigens preferentially derive from unmutated genomic sequences in melanoma and non-small cell lung cancer.

Nat Cancer. 2025-5-22

[2]
Immunogenic cryptic peptides dominate the antigenic landscape of ovarian cancer.

Sci Adv. 2025-2-21

本文引用的文献

[1]
Breast cancer immunopeptidomes contain numerous shared tumor antigens.

J Clin Invest. 2024-1-2

[2]
Immune Surveillance of Acute Myeloid Leukemia Is Mediated by HLA-Presented Antigens on Leukemia Progenitor Cells.

Blood Cancer Discov. 2023-11-1

[3]
Machine learning methods and harmonized datasets improve immunogenic neoantigen prediction.

Immunity. 2023-11-14

[4]
BamQuery: a proteogenomic tool to explore the immunopeptidome and prioritize actionable tumor antigens.

Genome Biol. 2023-8-15

[5]
Unlocking the potential of microfluidics in mass spectrometry-based immunopeptidomics for tumor antigen discovery.

Cell Rep Methods. 2023-6-26

[6]
The immunopeptidome landscape associated with T cell infiltration, inflammation and immune editing in lung cancer.

Nat Cancer. 2023-5

[7]
Cancer's Dark Matter: Lighting the Abyss Unveils Universe of New Therapies.

Clin Cancer Res. 2023-6-13

[8]
Single immunizations of self-amplifying or non-replicating mRNA-LNP vaccines control HPV-associated tumors in mice.

Sci Transl Med. 2023-3-8

[9]
Exploring the Immunogenicity of Noncanonical HLA-I Tumor Ligands Identified through Proteogenomics.

Clin Cancer Res. 2023-6-13

[10]
Cancer statistics, 2023.

CA Cancer J Clin. 2023-1

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