Vaccination guidelines for patients treated for hematological diseases are typically conservative. Given their high risk for severe coronavirus infectious disease 2019 (COVID-19) it is important to identify those patients that benefit from vaccination. We prospectively quantified serum IgG antibodies to spike subunit 1 (S1) antigens during and after 2-dose mRNA-1273 (Spikevax/Moderna) vaccination in hematology patients. Obtaining S1 IgG ≥300 binding antibody units (BAU)/ml was considered adequate as it represents the lower level of S1 IgG concentration obtained in healthy individuals and it correlates with potent virus neutralization. Selected patients (n=723) were severely immunocompromised due to their disease or treatment thereof. Nevertheless, more than 50% of patients obtained S1 IgG ≥300 BAU/ml after 2-dose mRNA-1273. All patients with sickle cell disease or chronic myeloid leukemia obtained adequate antibody concentrations. Around 70% of patients with chronic graft versus host disease (GvHD), multiple myeloma, or untreated chronic lymphocytic leukemia (CLL) obtained S1 IgG ≥300 BAU/ml. Ruxolitinib or hypomethylating therapy but not high-dose chemotherapy blunted responses in myeloid malignancies. Responses in lymphoma patients, CLL patients on ibrutinib, and chimeric antigen receptor T cell recipients were low. The minimal time-interval after autologous hematopoietic cell transplantation (HCT) to reach adequate concentrations was <2 months for multiple myeloma, 8 months for lymphoma, and 4-6 months after allogeneic HCT. Serum IgG4, absolute B and NK cell number and number of immunosuppressants predicted S1 IgG ≥300 BAU/ml. Hematology patients on chemotherapy, shortly after HCT, or with chronic GvHD should not be precluded from vaccination. Netherlands Trial Register NL9553.

Lymph nodes (LNs) aid the interaction between lymphocytes and antigenpresenting cells, resulting in adequate and prolonged adaptive immune responses. LN stromal cells (LNSCs) are crucially involved in steering adaptive immune responses at different levels. Most knowledge on LNSCs has been obtained from mouse studies, and few studies indicate similarities with their human counterparts. Recent advances in single-cell technologies have revealed significant LNSC heterogeneity among different subsets with potential selective functions in immunity. This review provides an overview of current knowledge of LNSCs based on human and murine studies describing the role of these cells in health and disease. LNSCs as orchestrators of the immune systemLNs are specialized secondary lymphoid organs (SLOs) that are essential for the initiation of adaptive immunity. Most cells within LNs are lymphocytes that continuously enter the LN from the bloodstream. The afferent lymph transports antigens and antigen-presenting cells (APCs; see Glossary) to the LN, which creates an environment in which antigen-specific lymphocytes and APCs can optimally interact, resulting in adequate and prolonged immune responses [1]. The architecture of the LN is pivotal for its role in inducing humoral immune responses, and this is created and supported by LNSCs (Box 1) [2]. LNSCs create a 3D network that generates a backbone for immune cells to migrate on, and thus, during the time lymphocytes reside in the LN, they extensively interact with stromal cells. In addition to providing structural support, LNSCs also provide survival signals, nutrients, soluble factors, and antigens that are collectively required for immunosurveillance as well as for the generation and control of adaptive immune responses [3,4]. Therefore, understanding the immunobiology of LNSCs is key to comprehending specific aspects of the immune system more fully. The aim of this review is to provide an overview of the current state of knowledge about murine and human LNSC subsets and functions. We discuss recent findings regarding human and mouse LNSCs under homeostatic conditions, and describe their immunomodulatory capacities during autoimmunity, infection, and cancer. We anticipate that some of these findings may fuel further investigations into the field of LN biology and immune defense across species. HighlightsSingle-cell RNA sequencing has uncovered conspicuous heterogeneity in lymph node stromal cells (LNSCs) populations in mice and humans.Human and mouse LNSC subsets show similarities in their transcriptomic profiles and trajectory analyses.Each LNSC subset has its own specific function in regulating immune responses.Human LNSCs have the machinery to regulate peripheral tolerance, making them attractive targets for modulating tolerance induction and maintenance.LNSCs in mice and humans can suppress T cell proliferation during strong inflammatory stimuli. Different mechanisms are utilized to perform this function.LNSCs from patients with particular autoimmune diseases exhibit alte...