The Role of Single-Cell Profiling and Deep Immunophenotyping in Understanding Immune Therapy Cardiotoxicity

Yuhsin Vivian Huang^{1

2}, Sarah Waliany³, Daniel Lee¹, Francisco X Galdos^{1

4}, Ronald M Witteles^{1

3

5}, Joel W Neal^{3

6

7}, Alice C Fan^{3

6

7}, Holden T Maecker^{8

9}, Patricia K Nguyen^{1

3

5}, Sean M Wu^{1

3

5}, Han Zhu^{1

3

5}

Affiliations

¹ Stanford Cardiovascular Institute, Stanford University, Stanford, California, USA.
² Cornell University, Ithaca, New York, USA.
³ Department of Medicine, Stanford University School of Medicine, Stanford, California, USA.
⁴ Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, California, USA.
⁵ Division of Cardiovascular Medicine, Stanford University School of Medicine, Stanford, California, USA.
⁶ Division of Oncology, Stanford University School of Medicine, Stanford, California, USA.
⁷ Stanford Cancer Institute, Stanford University, Stanford, California, USA.
⁸ Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, California, USA.
⁹ Institute for Immunity, Transplantation and Infection, Stanford University School of Medicine, Stanford, California, USA.

PMID: 36636436
PMCID: PMC9830194
DOI: 10.1016/j.jaccao.2022.08.012

Review

The Role of Single-Cell Profiling and Deep Immunophenotyping in Understanding Immune Therapy Cardiotoxicity

Yuhsin Vivian Huang et al. JACC CardioOncol. 2022.

. 2022 Dec 20;4(5):629-634.

doi: 10.1016/j.jaccao.2022.08.012. eCollection 2022 Dec.

Authors

Affiliations

¹ Stanford Cardiovascular Institute, Stanford University, Stanford, California, USA.
² Cornell University, Ithaca, New York, USA.
³ Department of Medicine, Stanford University School of Medicine, Stanford, California, USA.
⁴ Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, California, USA.
⁵ Division of Cardiovascular Medicine, Stanford University School of Medicine, Stanford, California, USA.
⁶ Division of Oncology, Stanford University School of Medicine, Stanford, California, USA.
⁷ Stanford Cancer Institute, Stanford University, Stanford, California, USA.
⁸ Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, California, USA.
⁹ Institute for Immunity, Transplantation and Infection, Stanford University School of Medicine, Stanford, California, USA.

PMID: 36636436
PMCID: PMC9830194
DOI: 10.1016/j.jaccao.2022.08.012

No abstract available

Keywords: CITE-seq, cellular indexing of transcriptomes and epitopes by sequencing; CTLA-4, cytotoxic T-lymphocyte antigen 4; CyTOF, time-of-flight mass cytometry; ICI, immune checkpoint inhibitor; IRAE, immune-related adverse event; PD-1, programmed death-1; immunotherapy; mass cytometry; monoclonal antibody; myocarditis; scRNA-seq, single-cell RNA sequencing; scTCR-seq, single-cell T-cell receptor sequencing; treatment.

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Conflict of interest statement

This work was supported by National Institutes of Health grant 1K08HL16140501; a Sarnoff Scholar Career Development Award; National Institute of General Medical Sciences grant 1RM1 GM131981-02; an American Heart Association Established Investigator Award; the Hoffmann/Schroepfer Foundation; the Additional Venture Foundation; the Joan and Sanford I. Weill Scholar Fund; an iAward grant from Sanofi US; National Heart, Lung, and Blood Institute grant R01HL13483004; and American Heart Association grant AW849785 (Transformative Award). Dr Wu has received funding from Sanofi. Dr Witteles sits on advisory boards for Pfizer, Alnylam, Ionis/Akcea, Eidos, and Intelia. Dr Neal has served in a consulting or an advisory role for AstraZeneca, Genentech/Roche, Exelixis, Jounce Therapeutics, Takeda Pharmaceuticals, Eli Lilly, Calithera Biosciences, Amgen, Iovance, Biotherapeutics, Blueprint Pharmaceuticals, Regeneron Pharmaceuticals, and Natera; and has received research funding from Genentech/Roche, Merck, Novartis, Boehringer Ingelheim, Exelixis, Nektar Therapeutics, Takeda Pharmaceuticals, Adaptimmune, GlaxoSmithKline, Janssen, and AbbVie. Dr Waliany has received consulting fees from AstraZeneca. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.

Figures

**Figure 1**
Single-Cell Multiomics in Immunotherapy-Induced Cardiotoxicity Bench-to-bedside work flow using multiomics on patient samples with immune checkpoint inhibitor (ICI)–induced cardiotoxicity and corresponding ICI-induced myocarditis mouse models. CITE = cellular indexing of transcriptomes and epitopes; irAE = immune-related adverse event; mRNA = messenger RNA; PBMC = peripheral blood mononuclear cell; scRNA = single-cell RNA; TCR = T-cell receptor.

See this image and copyright information in PMC

References

1. Waliany S., Lee D., Witteles R.M., et al. Immune checkpoint inhibitor cardiotoxicity: understanding basic mechanisms and clinical characteristics and finding a cure. Annu Rev Pharmacol Toxicol. 2021;61:113–134. doi: 10.1146/ANNUREV-PHARMTOX-010919-023451. - DOI - PubMed
1. Liu J., Qu S., Zhang T., et al. Applications of single-cell omics in tumor immunology. Front Immunol. 2021;12 doi: 10.3389/FIMMU.2021.697412. - DOI - PMC - PubMed
1. Wang M., Gu M., Liu L., Liu Y., Tian L. Single-cell RNA sequencing (scRNA-seq) in cardiac tissue: applications and limitations. Vasc Health Risk Manag. 2021;17:641. doi: 10.2147/VHRM.S288090. - DOI - PMC - PubMed
1. Gao C., Zhang M., Chen L. The comparison of two single-cell sequencing platforms: bd rhapsody and 10X Genomics Chromium. Curr Genomics. 2020;21(8):602. doi: 10.2174/1389202921999200625220812. - DOI - PMC - PubMed
1. Johnson D.B., Balko J.M., Compton M.L., et al. Fulminant myocarditis with combination immune checkpoint blockade. N Engl J Med. 2016;375(18):1749–1755. doi: 10.1056/NEJMoa1609214. - DOI - PMC - PubMed

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The Role of Single-Cell Profiling and Deep Immunophenotyping in Understanding Immune Therapy Cardiotoxicity

Affiliations

The Role of Single-Cell Profiling and Deep Immunophenotyping in Understanding Immune Therapy Cardiotoxicity

Authors

Affiliations

Conflict of interest statement

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References

Publication types

Grants and funding

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