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Updated: Jan 30, 2026
Development of a 68Gallium-Labeled D-Peptide PET Tracer for Imaging Programmed Death-Ligand 1 Expression
Published on: February 3, 2023
Programmed Cell Death 1 Ligand 1 and Programmed Cell Death 1 Ligand 2 Are Expressed in Conjunctival Invasive Squamous
Natalie Wolkow1, Frederick A Jakobiec2, Amir H Afrogheh3
1David G. Cogan Ophthalmic Pathology Laboratory, Department of Ophthalmology, Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, Massachusetts, USA; Division of Ophthalmic Plastic and Reconstructive Surgery, Department of Ophthalmology, Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, Massachusetts, USA.
Purpose:
Novel cancer immunotherapies, called immune checkpoint inhibitors, have demonstrated clinical efficacy in the treatment of squamous cell carcinomas of the head and neck. Tissue expression of programmed cell death 1 ligand 1 (PD-L1) and programmed cell death 1 ligand 2 (PD-L2) has been shown to predict tumor response to these drugs. We examine the expression of prognostic immune biomarkers, PD-L1 and PD-L2, in invasive ocular surface squamous neoplasia.
Design:
Retrospective case series.
Methods:
Eighteen cases of ocular surface or ocular adnexal invasive squamous cell carcinomas were identified in pathology case files of the Massachusetts General Hospital/Massachusetts Eye and Ear Infirmary and at the Wills Eye Hospital accessioned between January 1, 2014 and January 1, 2017. Immunohistochemical staining for PD-L1, PD-L2, CD8, and p16 was performed and graded in a standardized fashion.
Results:
PD-L1 and PD-L2 were expressed on tumor cells to varying degrees, and also on some stromal cells and endothelial cells. Stromal and endothelial cell expression was also seen in control conjunctival specimens. Tumor expression of PD-L1 and PD-L2 was present on the cell membranes. All 18 (100%) of the tumors expressed PD-L1: 7 (39%) expressed a high level, 3 (17%) expressed a medium level, and 8 (44%) expressed a low level. Only 9 (50%) tumors expressed PD-L2 and it was at a low level. The expression of PD-L1 in tumor cells correlated with the presence of CD8-positive cytotoxic T lymphocytes among tumor cells (P < .01) and with the presence of CD8-positive cells in the surrounding stroma (P = .04).
Conclusions:
A subset of ocular invasive conjunctival squamous carcinomas express high levels of PD-L1 and CD8 and therefore may respond therapeutically to immune checkpoint inhibition.
Insights
Ocular squamous cell carcinomas express PD-L1, a biomarker for immune checkpoint inhibitors. High PD-L1 and CD8 expression in tumors suggests potential response to these novel cancer therapies.
Area of Science:
- Oncology
- Immunology
- Ophthalmology
Background:
- Immune checkpoint inhibitors are effective for head and neck squamous cell carcinomas.
- Programmed cell death 1 ligand 1 (PD-L1) and programmed cell death 1 ligand 2 (PD-L2) expression predicts response to these therapies.
- Ocular surface squamous neoplasia is a relevant cancer for this research.
Purpose of the Study:
- To examine the expression of PD-L1 and PD-L2 in invasive ocular surface squamous neoplasia.
- To determine if these biomarkers correlate with tumor characteristics and immune cell infiltration.
Main Methods:
- Retrospective case series of 18 patients with ocular surface or adnexal invasive squamous cell carcinomas.
- Immunohistochemical staining for PD-L1, PD-L2, CD8, and p16.
- Standardized grading of biomarker expression.
Main Results:
- All 18 tumors (100%) expressed PD-L1 at varying levels (7 high, 3 medium, 8 low).
- 50% of tumors expressed PD-L2 at a low level.
- PD-L1 expression correlated with the presence of CD8-positive cytotoxic T lymphocytes in tumor and stromal cells.
Conclusions:
- A subset of ocular invasive conjunctival squamous carcinomas express high levels of PD-L1 and CD8.
- These tumors may be candidates for therapeutic immune checkpoint inhibition.
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