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Novel Protocol for Generating Physiologic Immunogenic Dendritic Cells

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Targeting YTHDF2/MDSCs to improve radiotherapy.

Xiaolan Deng¹, Ying Qing¹, Jianjun Chen²

¹Department of Systems Biology, Beckman Research Institute of City of Hope, Monrovia, CA 91016, USA.

Cell Chemical Biology

|July 21, 2023

Summary

This summary is machine-generated.

Ionizing radiation triggers YTHDF2 in myeloid-derived suppressor cells, hindering radiotherapy. Targeting YTHDF2 (YTH domain-containing family protein 2) overcomes this immunosuppression, improving cancer treatment outcomes.

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Area of Science:

Oncology
Immunology
Molecular Biology

Background:

Tumor immunosuppression is a significant barrier to effective radiotherapy.
The precise molecular mechanisms underlying radiation-induced immunosuppression remain incompletely understood.

Purpose of the Study:

To elucidate the role of YTHDF2 in mediating immunosuppression during radiotherapy.
To investigate the potential of targeting YTHDF2 to enhance radiotherapy efficacy.

Main Methods:

Investigated the effect of ionizing radiation (IR) on YTHDF2 expression in myeloid-derived suppressor cells (MDSCs).
Utilized genetic depletion and pharmacological inhibition of YTHDF2 in preclinical models.
Assessed the impact of YTHDF2 modulation on MDSC expansion, migration, and tumor immune microenvironment.

Main Results:

Ionizing radiation was found to induce YTHDF2 expression in MDSCs through an IR-YTHDF2-NF-κB signaling pathway.
This induction promoted MDSC expansion and migration, contributing to radiotherapy failure.
Genetic or pharmacological inhibition of YTHDF2 reversed these immunosuppressive effects.

Conclusions:

YTHDF2 plays a critical role in mediating radiation-induced immunosuppression by promoting MDSC functions.
Targeting YTHDF2 represents a promising strategy to overcome treatment resistance and improve radiotherapy outcomes in cancer patients.