Changes of peripheral T cell subsets in melanoma patients with immune-related adverse events

Benjamin Müller; Anne Bärenwaldt; Petra Herzig; Alfred Zippelius; Lara Valeska Maul; Viviane Hess; David König; Heinz Läubli

doi:10.3389/fimmu.2023.1125111

Changes of peripheral T cell subsets in melanoma patients with immune-related adverse events

Front Immunol. 2023 Apr 12:14:1125111. doi: 10.3389/fimmu.2023.1125111. eCollection 2023.

Authors

Benjamin Müller¹, Anne Bärenwaldt¹, Petra Herzig¹, Alfred Zippelius^{1

2}, Lara Valeska Maul³, Viviane Hess², David König^{1

2}, Heinz Läubli^{1

2}

Affiliations

¹ Laboratory for Cancer Immunotherapy and Immunology, Department of Biomedicine, University of Basel, Basel, Switzerland.
² Division of Oncology, University Hospital Basel, Basel, Switzerland.
³ Department of Dermatology, University Hospital Basel, Basel, Switzerland.

Abstract

Introduction: Immunotherapies have improved the prognosis of many cancer patients including patients with advanced melanoma. Immune checkpoint receptors including CTLA-4 and PD-1 have been established as main therapeutic targets for immunotherapy of melanoma. Although monotherapy is effective in melanoma patients, a dual therapy approach has been shown to be most effective. Dual checkpoint blockade, however, increases substantially the risk for immune-related adverse events (irAEs).

Methods: In this study, we characterized peripheral immune cell subsets in patients with anti-PD-1 monotherapy and with dual immune receptors blockade targeting PD-1 and CTLA-4.

Results: We found differences in peripheral T cells between patients who developed severe immune-related side effects and patients with mild irAEs. We identified several mainly changes in CD8⁺ T cell subsets in patients with severe irAE under dual PD-1 and CTLA-4 blockade.

Discussion: This work suggests that peripheral immune cell dynamics could be associated with severe immune-related side effects in patients receiving immune checkpoint inhibitors. These changes could be used as future biomarkers in early diagnosis of irAEs.

Keywords: CTLA-4; PD-1; cancer immunotherapy; colitis; hepatitis; immune checkpoint.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Biomarkers
CTLA-4 Antigen* / antagonists & inhibitors
Drug Therapy, Combination
Female
Humans
Immune Checkpoint Inhibitors* / adverse effects
Immune Checkpoint Inhibitors* / therapeutic use
Immunotherapy / methods
Male
Melanoma* / immunology
Melanoma* / therapy
Programmed Cell Death 1 Receptor* / antagonists & inhibitors
T-Lymphocyte Subsets* / drug effects
T-Lymphocyte Subsets* / immunology

Substances

CTLA-4 Antigen
Immune Checkpoint Inhibitors
Programmed Cell Death 1 Receptor
Biomarkers

Grants and funding

This work was supported by funding from the Swiss National Science Foundation (SNSF grant #310030-184720 to HL).