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Updated: Dec 4, 2025
Immunohistochemical Staining of B7-H1 PD-L1 on Paraffin-embedded Slides of Pancreatic Adenocarcinoma Tissue
Published on: January 3, 2013
Vestigial-like 1 is a shared targetable cancer-placenta antigen expressed by pancreatic and basal-like breast cancers
Sherille D Bradley1, Amjad H Talukder1, Ivy Lai1
1Department of Melanoma Medical Oncology, UT MD Anderson Cancer Center, Houston, TX, USA.
Abstract:
Cytotoxic T lymphocyte (CTL)-based cancer immunotherapies have shown great promise for inducing clinical regressions by targeting tumor-associated antigens (TAA). To expand the TAA landscape of pancreatic ductal adenocarcinoma (PDAC), we performed tandem mass spectrometry analysis of HLA class I-bound peptides from 35 PDAC patient tumors. This identified a shared HLA-A*0101 restricted peptide derived from co-transcriptional activator Vestigial-like 1 (VGLL1) as a putative TAA demonstrating overexpression in multiple tumor types and low or absent expression in essential normal tissues. Here we show that VGLL1-specific CTLs expanded from the blood of a PDAC patient could recognize and kill in an antigen-specific manner a majority of HLA-A*0101 allogeneic tumor cell lines derived not only from PDAC, but also bladder, ovarian, gastric, lung, and basal-like breast cancers. Gene expression profiling reveals VGLL1 as a member of a unique group of cancer-placenta antigens (CPA) that may constitute immunotherapeutic targets for patients with multiple cancer types.
Insights
Researchers identified Vestigial-like 1 (VGLL1) as a promising cancer antigen. VGLL1-specific T cells effectively targeted multiple cancer types, including pancreatic ductal adenocarcinoma (PDAC), offering new immunotherapy potential.
Area of Science:
- Immunology
- Oncology
- Molecular Biology
Background:
- Cytotoxic T lymphocyte (CTL)-based immunotherapies show promise in cancer treatment by targeting tumor-associated antigens (TAA).
- Identifying novel TAAs is crucial for expanding effective cancer immunotherapies, particularly for pancreatic ductal adenocarcinoma (PDAC).
Purpose of the Study:
- To identify novel tumor-associated antigens (TAAs) for pancreatic ductal adenocarcinoma (PDAC) and other cancers.
- To evaluate the potential of Vestigial-like 1 (VGLL1) as a shared cancer-placenta antigen (CPA) for immunotherapy.
Main Methods:
- Tandem mass spectrometry was used to analyze HLA class I-bound peptides from 35 PDAC tumors.
- VGLL1-specific CTLs were expanded from patient blood and tested against various allogeneic tumor cell lines.
- Gene expression profiling was performed to characterize VGLL1 and its associated antigen group.
Main Results:
- A shared HLA-A*0101-restricted peptide derived from Vestigial-like 1 (VGLL1) was identified as a putative TAA.
- VGLL1 is overexpressed in multiple tumor types but shows low or absent expression in essential normal tissues.
- VGLL1-specific CTLs recognized and killed a majority of HLA-A*0101 allogeneic tumor cell lines from PDAC, bladder, ovarian, gastric, lung, and basal-like breast cancers.
Conclusions:
- Vestigial-like 1 (VGLL1) represents a promising shared tumor-associated antigen (TAA) for diverse cancer types.
- VGLL1 is a member of a unique group of cancer-placenta antigens (CPAs) with significant immunotherapeutic potential.
- Targeting VGLL1 could offer a broad-spectrum immunotherapy strategy for patients with various malignancies.
