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Research Article: Cytokine-responsive T- and NK-cells portray SARS-CoV-2 vaccine-responders and infection in multiple myeloma patients

Date Published: 2023-12-04

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-?-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.

Introduction:
During the COVID-19 pandemic, patients with multiple myeloma (MM) were among the first to receive mRNA-based SARS-CoV-2 vaccines [1]. Immunological responses to SARS-CoV-2 vaccination and breakthrough infection (BTI) in patients with hematological malignancies have been extensively analyzed [2,3,4,5,6,7,8]. Patients with MM exhibited heterogeneous serological and T-cell vaccination responses against SARS-CoV-2 [9,10,11,12,13,14]. Sufficient immune response is associated with strong neutralizing antibodies with…

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