A Novel Potential Role for Monocytes Revealed by Single Cell Analysis of Immunotherapy Induced Immune Related Adverse Events

Zachary Garrison; Matthew Chang; Noah Hornick; Wesley Y Yu; Jeffrey B Cheng; Rajan P Kulkarni

doi:10.3390/cancers14215407

A Novel Potential Role for Monocytes Revealed by Single Cell Analysis of Immunotherapy Induced Immune Related Adverse Events

Cancers (Basel). 2022 Nov 2;14(21):5407. doi: 10.3390/cancers14215407.

Authors

Zachary Garrison¹, Matthew Chang¹, Noah Hornick¹, Wesley Y Yu¹, Jeffrey B Cheng^{2

3}, Rajan P Kulkarni^{1

4

5

6}

Affiliations

¹ Department of Dermatology, Oregon Health & Science University, Portland, OR 97239, USA.
² Department of Dermatology, University of California San Francisco (UCSF), San Francisco, CA 94143, USA.
³ Department of Dermatology, Veterans Affairs Medical Center, San Francisco, CA 94121, USA.
⁴ Knight Cancer Institute, Oregon Health and Science University, Portland, OR 97239, USA.
⁵ Operative Care Division, U.S. Department of Veterans Affairs Portland Health Care System, Portland, OR 97239, USA.
⁶ Cancer Early Detection Advanced Research Center (CEDAR), 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.

Keywords: autoimmunity; cancer; immune checkpoint blockade; immune related adverse event; immunotherapy; inflammation.

Grants and funding

This research was funded by the following sources: The Cancer Research Institute, Clinic & Laboratory Integration Program (CLIP), The Collins Medical Trust, The American Cancer Society, grant numbers 129523-MRSG-16-029-01-DDC and TLC-21-003-01-TLC, The Department of Defense (DOD) Congressionally Directed Medical Research Program (CDMRP) grant numbers W81XWH-17-1-0514, W81XWH-17-1-0098, and W81XWH-21-1-0818, The Melanoma Research Alliance, grant number 344442, The OHSU Physician-Scientist Program, and the Cancer Advanced Research Early Detection Center (CEDAR) at OHSU.