CD4 T cells and toxicity from immune checkpoint blockade.
Noah J EarlandWubing ZhangAbul UsmaniAishwarya NeneAntonella BacchiocchiDavid Y ChenMario SznolRuth HalabanAadel A ChaudhuriAaron M NewmanPublished in: Immunological reviews (2023)
Immune-related toxicities, otherwise known as immune-related adverse events (irAEs), occur in a substantial fraction of cancer patients treated with immune checkpoint inhibitors (ICIs). Ranging from asymptomatic to life-threatening, ICI-induced irAEs can result in hospital admission, high-dose corticosteroid treatment, ICI discontinuation, and in some cases, death. A deeper understanding of the factors underpinning severe irAE development will be essential for improved irAE prediction and prevention, toward maximizing the benefits and safety profiles of ICIs. In recent work, we applied mass cytometry, single-cell RNA sequencing, single-cell V(D)J sequencing, bulk RNA sequencing, and bulk T-cell receptor (TCR) sequencing to identify pretreatment determinants of severe irAE development in patients with advanced melanoma. Across 71 patients separated into three cohorts, we found that two baseline features in circulation-elevated activated CD4 effector memory T-cell abundance and TCR diversity-are associated with severe irAE development, independent of the affected organ system within 3 months of ICI treatment initiation. Here, we provide an extended perspective on this work, synthesize and discuss related literature, and summarize practical considerations for clinical translation. Collectively, these findings lay a foundation for data-driven and mechanistic insights into irAE development, with the potential to reduce ICI morbidity and mortality in the future.
Keyphrases
- single cell
- rna seq
- high dose
- high throughput
- end stage renal disease
- early onset
- regulatory t cells
- systematic review
- chronic kidney disease
- low dose
- healthcare
- newly diagnosed
- emergency department
- ejection fraction
- prognostic factors
- oxidative stress
- high glucose
- working memory
- microbial community
- patient reported outcomes
- electronic health record
- immune response
- papillary thyroid
- replacement therapy
- antibiotic resistance genes