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Immune Checkpoint Inhibition in Hodgkin Lymphoma
1Lymphoma Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY.
Abstract:
Intricate systems of checkpoints such as the programmed cell death protein 1 (PD-1)/programmed death ligand 1 (PD-L1) axis regulate adaptive immune responses to protect against tissue damage. However, diverse cancers can exploit these pathways to evade or suppress antitumor immunity, leading to tumor progression. Correspondingly, immune checkpoint inhibitors that block PD-1/PD-L1 signaling have shown marked therapeutic efficacy in certain cancers, such as Hodgkin lymphoma. Reed-Sternberg cells, the hallmark cells of Hodgkin lymphoma, commonly overexpress PD-1 ligands, and recent clinical trials have demonstrated impressive response rates with the PD-1 inhibitors nivolumab and pembrolizumab in relapsed or refractory Hodgkin lymphoma, leading to their FDA approval in this setting. Current efforts are underway to improve clinical responses by incorporating PD-1 inhibitors into earlier treatment regimens and identifying therapeutic agents that synergize with PD-1 inhibitors. This review summarizes our understanding of the PD-1/PD-L1 axis in Hodgkin lymphoma, recent clinical studies of anti-PD-1 monotherapy and promising combination immunotherapy in the pipeline.
Insights
Immune checkpoint inhibitors targeting the PD-1/PD-L1 axis show significant efficacy in Hodgkin lymphoma by blocking tumor evasion. Research is exploring combination immunotherapies to enhance treatment responses.
Area of Science:
- Immunology
- Oncology
- Cancer Research
Background:
- Adaptive immune responses are regulated by checkpoints like the PD-1/PD-L1 axis.
- Cancers, including Hodgkin lymphoma, can exploit these checkpoints to evade immune surveillance.
- Reed-Sternberg cells in Hodgkin lymphoma often overexpress PD-1 ligands.
Purpose of the Study:
- To review the role of the PD-1/PD-L1 axis in Hodgkin lymphoma.
- To summarize recent clinical studies on anti-PD-1 monotherapy.
- To discuss promising combination immunotherapies for Hodgkin lymphoma.
Main Methods:
- Review of existing literature on PD-1/PD-L1 signaling in cancer.
- Analysis of clinical trial data for PD-1 inhibitors in Hodgkin lymphoma.
- Exploration of preclinical and clinical data on combination immunotherapies.
Main Results:
- PD-1 inhibitors (nivolumab, pembrolizumab) demonstrate high response rates in relapsed/refractory Hodgkin lymphoma.
- These agents are FDA-approved for specific Hodgkin lymphoma settings.
- Ongoing research focuses on earlier treatment integration and synergistic combinations.
Conclusions:
- The PD-1/PD-L1 axis is a critical target in Hodgkin lymphoma therapy.
- Anti-PD-1 monotherapy offers a valuable treatment option.
- Combination strategies hold promise for improving outcomes in Hodgkin lymphoma.
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