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Predicting In Vivo Payloads Delivery using a Blood-brain Tumor-barrier in a Dish

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Stromal barriers to the abscopal effect.

Tian V Tian¹, Silvia Affò²

¹Upper GI and Endocrine Tumor Unit, Vall d'Hebron Institute of Oncology (VHIO), Hospital Universitari Vall d'Hebron, Vall d'Hebron Barcelona Hospital Campus, C/ Natzaret, 115-117, 08035 Barcelona, Spain.

|May 13, 2025

Summary

This summary is machine-generated.

Cancer-associated fibroblasts expressing high levels of SFRP2 reduce radioimmunotherapy

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Area of Science:

Oncology
Immunology
Cancer Biology

Background:

Radioimmunotherapy (RAIT) shows promise but is limited by the tumor microenvironment.
Cancer-associated fibroblasts (CAFs) play a critical role in shaping the tumor microenvironment.
Specific CAF subtypes may impede therapeutic efficacy.

Purpose of the Study:

To investigate the role of specific CAFs in limiting the abscopal effect of RAIT.
To identify molecular targets within CAFs to enhance RAIT response.

Main Methods:

Analysis of tumor microenvironment in preclinical models.
Investigated the role of Plasminogen Activator Inhibitor-1 (PAI-1) and Secreted Frizzled-Related Protein 2 (SFRP2).
Assessed the impact of targeting PAI-1 and SFRP2 on T cell infiltration and RAIT efficacy.

Main Results:

PAI-1-induced SFRP2-high CAFs were found to suppress the abscopal effect of RAIT.
Targeting PAI-1 or SFRP2 led to enhanced T cell recruitment to tumors.
Inhibition of these CAFs prevented the formation of an immunosuppressive perivascular niche.

Conclusions:

SFRP2-high CAFs driven by PAI-1 are key suppressors of RAIT's abscopal effect.
Targeting PAI-1 or SFRP2 represents a promising strategy to improve RAIT outcomes.
Modulating the CAF-mediated immunosuppressive niche can enhance anti-tumor immunity during RAIT.