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T cell characteristics associated with toxicity to immune checkpoint blockade in patients with melanoma
- Source :
- Nature Medicine; February 2022, Vol. 28 Issue: 2 p353-362, 10p
- Publication Year :
- 2022
-
Abstract
- Severe immune-related adverse events (irAEs) occur in up to 60% of patients with melanoma treated with immune checkpoint inhibitors (ICIs). However, it is unknown whether a common baseline immunological state precedes irAE development. Here we applied mass cytometry by time of flight, single-cell RNA sequencing, single-cell V(D)J sequencing, bulk RNA sequencing and bulk T cell receptor (TCR) sequencing to study peripheral blood samples from patients with melanoma treated with anti-PD-1 monotherapy or anti-PD-1 and anti-CTLA-4 combination ICIs. By analyzing 93 pre- and early on-ICI blood samples and 3 patient cohorts (n= 27, 26 and 18), we found that 2 pretreatment factors in circulation—activated CD4 memory T cell abundance and TCR diversity—are associated with severe irAE development regardless of organ system involvement. We also explored on-treatment changes in TCR clonality among patients receiving combination therapy and linked our findings to the severity and timing of irAE onset. These results demonstrate circulating T cell characteristics associated with ICI-induced toxicity, with implications for improved diagnostics and clinical management.
Details
- Language :
- English
- ISSN :
- 10788956 and 1546170X
- Volume :
- 28
- Issue :
- 2
- Database :
- Supplemental Index
- Journal :
- Nature Medicine
- Publication Type :
- Periodical
- Accession number :
- ejs58689792
- Full Text :
- https://doi.org/10.1038/s41591-021-01623-z