Cytokine-responsive T- and NK-cells portray SARS-CoV-2 vaccine-responders and infection in multiple myeloma patients.
Julius C EnssleJulia CampeAlina MoterIsabel VoitAlec GessnerWeijia YuSebastian WolfBjörn SteffenHubert ServeMelanie BremmSabine HueneckeMichael LohoffMaria VehreschildHolger F RabenauMarek WideraSandra CiesekThomas OellerichKatharina ImkellerMichael A RiegerIvana von MetzlerEvelyn UllrichPublished in: Leukemia (2023)
Patients with multiple myeloma (MM) routinely receive mRNA-based vaccines to reduce COVID-19-related mortality. However, whether disease- and therapy-related alterations in immune cells and cytokine-responsiveness contribute to the observed heterogeneous vaccination responses is unclear. Thus, we analyzed peripheral blood mononuclear cells from patients with MM during and after SARS-CoV-2 vaccination and breakthrough infection (BTI) using combined whole-transcriptome and surface proteome single-cell profiling with functional serological and T-cell validation in 58 MM patients. Our results demonstrate that vaccine-responders showed a significant overrepresentation of cytotoxic CD4 + T- and mature CD38 + NK-cells expressing FAS + /TIM3 + with a robust cytokine-responsiveness, such as type-I-interferon-, IL-12- and TNF-α-mediated signaling. Patients with MM experiencing BTI developed strong serological and cellular responses and exhibited similar cytokine-responsive immune cell patterns as vaccine-responders. This study can expand our understanding of molecular and cellular patterns associated with immunization responses and may benefit the design of improved vaccination strategies in immunocompromised patients.
Keyphrases
- sars cov
- end stage renal disease
- single cell
- nk cells
- chronic kidney disease
- newly diagnosed
- prognostic factors
- rheumatoid arthritis
- peritoneal dialysis
- coronavirus disease
- respiratory syndrome coronavirus
- stem cells
- patient reported outcomes
- coronary artery disease
- rna seq
- cardiovascular events
- risk factors
- genome wide
- gene expression
- mesenchymal stem cells
- intensive care unit
- cell therapy
- patient reported
- smoking cessation