PD-1 is a regulator of NY-ESO-1-specific CD8+ T cell expansion in melanoma patients
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Updated: Jun 23, 2026
Monitoring PD-1-Blocking Antibodies Bound to T Cells Derived from a Drop of Peripheral Blood
Published on: February 5, 2020
Julien Fourcade1, Pavol Kudela, Zhaojun Sun
1Department of Medicine and Division of Hematology/Oncology, University of Pittsburgh, School of Medicine, Pittsburgh, PA 15213, USA.
Abstract:
The programmed death 1 (PD-1) receptor is a negative regulator of activated T cells and is up-regulated on exhausted virus-specific CD8(+) T cells in chronically infected mice and humans. Programmed death ligand 1 (PD-L1) is expressed by multiple tumors, and its interaction with PD-1 resulted in tumor escape in experimental models. To investigate the role of PD-1 in impairing spontaneous tumor Ag-specific CD8(+) T cells in melanoma patients, we have examined the effect of PD-1 expression on ex vivo detectable CD8(+) T cells specific to the tumor Ag NY-ESO-1. In contrast to EBV, influenza, or Melan-A/MART-1-specific CD8(+) T cells, NY-ESO-1-specific CD8(+) T cells up-regulated PD-1 expression. PD-1 up-regulation on spontaneous NY-ESO-1-specific CD8(+) T cells occurs along with T cell activation and is not directly associated with an inability to produce cytokines. Importantly, blockade of the PD-1/PD-L1 pathway in combination with prolonged Ag stimulation with PD-L1(+) APCs or melanoma cells augmented the number of cytokine-producing, proliferating, and total NY-ESO-1-specific CD8(+) T cells. Collectively, our findings support the role of PD-1 as a regulator of NY-ESO-1-specific CD8(+) T cell expansion in the context of chronic Ag stimulation. They further support the use of PD-1/PD-L1 pathway blockade in cancer patients to partially restore NY-ESO-1-specific CD8(+) T cell numbers and functions, increasing the likelihood of tumor regression.
Insights
Programmed death 1 (PD-1) negatively regulates T cells. Blocking the PD-1/PD-L1 pathway can restore anti-tumor CD8(+) T cell function in melanoma patients, potentially enhancing tumor regression.
Area of Science:
- Immunology
- Cancer Biology
- T cell Exhaustion
Background:
- Programmed death 1 (PD-1) is a T cell negative regulator.
- PD-1 is upregulated on exhausted T cells during chronic infections.
- Tumor cells express PD-1 ligand (PD-L1), promoting tumor immune escape.
Purpose of the Study:
- Investigate PD-1's role in impairing tumor antigen-specific CD8(+) T cells in melanoma.
- Examine PD-1 expression on NY-ESO-1 specific CD8(+) T cells in melanoma patients.
Main Methods:
- Analyzed ex vivo PD-1 expression on NY-ESO-1 specific CD8(+) T cells.
- Compared PD-1 expression with other antigen-specific T cells (EBV, influenza, Melan-A/MART-1).
- Assessed the impact of PD-1/PD-L1 pathway blockade on T cell function.
Main Results:
- NY-ESO-1 specific CD8(+) T cells, unlike others, upregulated PD-1.
- PD-1 upregulation occurred with T cell activation, not cytokine production impairment.
- PD-1/PD-L1 blockade enhanced proliferation, cytokine production, and numbers of NY-ESO-1 specific CD8(+) T cells.
Conclusions:
- PD-1 regulates NY-ESO-1 specific CD8(+) T cell expansion under chronic antigen stimulation.
- PD-1/PD-L1 pathway blockade can restore anti-tumor T cell function in cancer.
- This approach may increase tumor regression likelihood in patients.
