ArticleFrontiers in pharmacology2025
Anti-CTLA-and anti-PD-1 immune checkpoint inhibitor antibodies impair human sperm motility
Article in Frontiers in pharmacology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
3 citing papers in PubMed.
- Impact of immunotherapy and small molecule cancer therapy on fertility: a narrative review of current evidence, mechanisms and future directions.BMJ oncology · 2026Review
- Testicular Function After Immune-Checkpoint Inhibitors Treatment.Clinical endocrinology · 2025Article
- The dual nature of immunotherapy in female reproductive disorders: immune homeostasis and clinical challenges.Frontiers in immunology · 2025Review
Corrections and comments
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Authors and funding
12 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Background: Immune checkpoint inhibitors (ICIs), namely, anti-cytotoxic T lymphocyte-associated protein 4 (CTLA-4) monoclonal antibody Ipilimumab and anti- and programmed cell death 1 (PD-1) monoclonal antibodies Nivolumab, and Pembrolizumab, have improved the treatment outcomes for many other cancer types. However, their impact on fertility remains under-explored. Methods: The possible direct effects of ICIs on human sperm was investigated. Spermatozoa from ten normozoospermic donors were exposed to Ipilimumab, Nivolumab, or Pembrolizumab at concentrations ranging from 1 to 100 ng/mL. Sperm motility was assessed through standard laboratory process. Cell viability and apoptosis markers were evaluated by flow-cytometry using fluorescent Annexin-V probe and Terminal Uridine Nick-End Label (TUNEL) assays. Protein-A-purified therapeutic antibodies (IgG) were also evaluated. Results: Spermatozoa had high PD-1 (>99%) and negligible CTLA-4 expression. Exposure to ICIs, was associated with a concentration-dependent impairment of sperm motility, noticeable for Pembrolizumab and Ipilimumab since 10 ng/mL, and for Nivolumab since 100 ng/mL. However, no significant effect on cell apoptosis or viability was shown. Purified IgG from ICIs maintained the adverse effect on cell motility without affecting viability. Conclusion: ICIs, specifically Pembrolizumab, Nivolumab, and Ipilimumab, adversely affect human sperm motility
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