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Barking up the right tree: Immune checkpoint signatures of human and dog cancers
Mikolaj Kocikowski1,2, Marcos Yébenes Mayordomo1, Javier Alfaro1,3,4
1International Centre for Cancer Vaccine Science, University of Gdansk, Gdansk, Poland.
Abstract:
In the quest for improved therapeutics targeting immune checkpoints (ICs), we turn to spontaneously developing dog (canine) cancers, some of which genetically and clinically mirror the human counterparts. Despite its potential, canine cancer immunology remains largely unexplored. Here, we examine the RNA-seq-based expression of 44 ICs across 14 canine cancer types and an extensive human dataset. We unveil diverse canine IC expression patterns and unique human IC signatures that reflect the histological type and primary site of cancer. We uncover a striking similarity between canine brain cancers, osteosarcoma, and their human counterparts, identifying them as prospective immunotherapy models. Four ICs - CD160, A2AR, NKG2A, and OX40 - are key to the differences observed between species. We also find that individual human IC signatures vary in how well they align with their respective cancer types, a pattern that may influence future approaches to personalized therapy. This exploration highlights aspects of canine and human cancer immunology that warrant further study, setting the stage for discoveries at their crossroads.
Insights
Canine cancers offer valuable insights into human immune checkpoint (IC) therapies. Researchers found similarities between dog and human brain cancers, suggesting dogs as potential models for immunotherapy research.
Area of Science:
- Comparative oncology
- Immunology
- Cancer research
Background:
- Immune checkpoints (ICs) are crucial targets for cancer therapeutics.
- Canine cancer immunology is an underexplored field with potential for translational research.
- Canine cancers share genetic and clinical similarities with human cancers.
Purpose of the Study:
- To investigate and compare immune checkpoint expression patterns in canine and human cancers.
- To identify potential canine cancer models for human immunotherapy research.
- To explore species-specific differences and similarities in immune checkpoint signatures.
Main Methods:
- Analysis of RNA-sequencing data for 44 immune checkpoints across 14 canine cancer types.
- Comparison with an extensive human cancer dataset.
- Identification of key immune checkpoints contributing to interspecies differences.
Main Results:
- Diverse canine immune checkpoint expression patterns were observed, varying by cancer type and primary site.
- Unique human immune checkpoint signatures were identified.
- A striking similarity was found between canine and human brain cancers and osteosarcomas, highlighting their potential as immunotherapy models.
- CD160, A2AR, NKG2A, and OX40 were identified as key immune checkpoints differentiating species.
- Variability in human immune checkpoint signatures relative to cancer types suggests implications for personalized therapy.
Conclusions:
- Canine cancer models show promise for advancing human cancer immunotherapy research.
- Comparative analysis of immune checkpoints reveals both shared and distinct features between canine and human cancers.
- Further research into canine and human cancer immunology at their intersection could yield significant discoveries for novel therapeutic strategies.
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