What question did this study set out to answer?

To identify and characterize the PD-1 interactome in osteosarcoma cells and evaluate its evolutionary conservation across species.

December 18, 2024Cell Communication and SignalingOpen Access

PD-1 interactome in osteosarcoma: identification of a novel PD-1/AXL interaction conserved between humans and dogs

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To identify and characterize the PD-1 interactome in osteosarcoma cells and evaluate its evolutionary conservation across species.
Assessed PD-1 expression and subcellular localization in human U2OS osteosarcoma cells using western blotting, flow cytometry, and immunofluorescence.
Profiled PD-1 protein partners using pull-down assays and quantitative mass spectrometry, confirming candidates with proximity ligation assays and immunoblotting.
Characterized binding interfaces and therapeutic inhibition using molecular dynamics simulations, PD-1 phosphorylation mutants, the AXL inhibitor bemcentinib, and canine osteosarcoma cell models.
Discovered a direct physical interaction between PD-1 and the receptor tyrosine kinase AXL, mediated strongly by both extracellular and intracellular domains.
Observed that treatment with the selective AXL inhibitor bemcentinib decreased PD-1/AXL binding affinity without completely abolishing the complex.
Confirmed endogenous co-expression and conserved binding of PD-1 and AXL in canine osteosarcoma cells, demonstrating cross-species conservation of the interacting residues.

Authors

KDKatarzyna DziubekUniversity of Gdańsk JFJakub FaktorUniversity of Gdańsk KLKiran Bharat LokhandeShiv Nadar University

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Implication

Preclinical study reveals a direct PD-1 and AXL receptor interaction in human and canine osteosarcoma cells, suggesting novel targets for improving bone cancer immunotherapy.

Cite This Study

Dziubek et al. (2024) studied this question.

synapsesocial.com/papers/6a7e4576dea41f5fbab7b12c https://doi.org/10.1186/s12964-024-01935-w

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Implication

Preclinical study reveals a direct PD-1 and AXL receptor interaction in human and canine osteosarcoma cells, suggesting novel targets for improving bone cancer immunotherapy.

PD-1 interactome in osteosarcoma: identification of a novel PD-1/AXL interaction conserved between humans and dogs

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Implication

Cite This Study

PD-1 interactome in osteosarcoma: identification of a novel PD-1/AXL interaction conserved between humans and dogs

Key Points

Discussion

Implication

Cite This Study

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