학술논문
Cytokine-responsive T- and NK-cells portray SARS-CoV-2 vaccine-responders and infection in multiple myeloma patients
Document Type
Original Paper
Author
Enssle, Julius C.; Campe, Julia; Moter, Alina; Voit, Isabel; Gessner, Alec; Yu, Weijia; Wolf, Sebastian; Steffen, Björn; Serve, Hubert; Bremm, Melanie; Huenecke, Sabine; Lohoff, Michael; Vehreschild, Maria; Rabenau, Holger F.; Widera, Marek; Ciesek, Sandra; Oellerich, Thomas; Imkeller, Katharina; Rieger, Michael A.; von Metzler, Ivana; Ullrich, Evelyn
Source
Leukemia. 38(1):168-180
Subject
Language
English
ISSN
0887-6924
1476-5551
1476-5551
Abstract
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.