A Novel Potential Role for Monocytes Revealed by Single Cell Analysis of Immunotherapy Induced Immune Related Adverse
Zachary Garrison1, Matthew Chang1, Noah Hornick1
1Department of Dermatology, Oregon Health & Science University, Portland, OR 97239, USA.
Abstract:
Immune related adverse events (irAEs) are one of the leading causes of discontinuation of cancer immunotherapy treatment. Despite extensive research into the frequency and types of irAEs, little is known about the cell types and pathways through which these drugs cause the observed side effects. To identify cell types and pathways of interest, we have analyzed single cell sequencing data of PBMCs from patients who developed skin irAEs as a result of their immunotherapy treatment. Using Azimuth's cell type identification software for PBMCs and GSEA pathway analysis, we found macrophage cell populations and reactive oxygen species related pathways to be upregulated. These results provide important groundwork to build a complete picture of the mechanisms which cause irAEs and finding ways to more effectively treat them.
Insights
Immune-related adverse events (irAEs) from cancer immunotherapy are common. This study identified specific macrophage populations and reactive oxygen pathways linked to skin irAEs, offering new targets for treatment.
Area of Science:
- Immunology
- Oncology
- Genomics
Background:
- Immune-related adverse events (irAEs) frequently lead to immunotherapy discontinuation in cancer patients.
- Understanding the cellular and molecular mechanisms underlying irAEs is crucial for effective management.
- Current knowledge on the specific cell types and pathways involved in irAE pathogenesis remains limited.
Purpose of the Study:
- To identify the specific cell types and molecular pathways implicated in the development of skin irAEs.
- To analyze single-cell sequencing data from patients experiencing immunotherapy-induced skin toxicities.
- To provide foundational insights into irAE mechanisms for improved therapeutic strategies.
Main Methods:
- Analysis of single-cell RNA sequencing data from peripheral blood mononuclear cells (PBMCs) of patients with skin irAEs.
- Utilized Azimuth software for precise identification of PBMC cell types.
- Employed Gene Set Enrichment Analysis (GSEA) to identify dysregulated molecular pathways.
Main Results:
- Upregulation of specific macrophage cell populations was observed in patients with skin irAEs.
- Enrichment of reactive oxygen species (ROS) related pathways was identified.
- These findings highlight key cellular players and molecular processes in irAE development.
Conclusions:
- Macrophage populations and ROS pathways are significantly associated with immunotherapy-induced skin irAEs.
- This research provides critical groundwork for understanding irAE mechanisms.
- Further investigation can lead to novel therapeutic approaches for managing irAEs and optimizing cancer immunotherapy.
