Publications by authors named "Michela Calvi"

Introduction: The lymphatic system is a multifaceted regulator of tissue homeostasis and an integral part of immune responses. Previous studies had shown that subsets of lymphatic endothelial cells (LEC) express , an essential component of humoral innate immunity and tissue homeostasis.

Methods: In the present study using whole-mount imaging and image-based morphometric quantifications, -targeted mice and functional analysis, we investigated the involvement of PTX3 in shaping and function of the lymphatic vasculature.

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γδ T cells provide rapid cellular immunity against pathogens. Here, we conducted matched single-cell RNA-sequencing and γδ-TCR-sequencing to delineate the molecular changes in γδ T cells during a longitudinal study following mRNA SARS-CoV-2 vaccination. While the first dose of vaccine primes Vδ2 T cells, it is the second administration that significantly boosts their immune response.

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  • Haploidentical hematopoietic stem cell transplantation (h-HSCT) is a treatment for blood cancers that relies on effective immune reconstitution (IR) to prevent severe infections like Human Cytomegalovirus (HCMV).
  • The study reveals that specific types of Natural Killer (NK) cells, called KIR NK cells, significantly contribute to controlling HCMV due to their early recovery and strong antiviral properties.
  • Maintaining high levels of KIR NK cells post-transplant can serve as a predictor for HCMV infection risk and could lead to improved treatments by boosting these immune cells in donor lymphocyte infusions.
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  • Higher frequencies of mucosal-associated invariant T (MAIT) cells are linked to a better immune response to the mRNA SARS-CoV-2 vaccine, with the hypothesis that TNF produced by these cells aids B cell activation after immunization.
  • A study analyzed peripheral blood mononuclear cells (PBMCs) from vaccinated adults at various time intervals following the Pfizer-BioNTech vaccine to explore the effects of repeated vaccinations on MAIT cells.
  • Results show that MAIT cells produce TNF in response to the vaccine, which boosts their proliferation and enhances anti-SARS-CoV-2 antibody production, especially activating memory B cells essential for long-term immunity.
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  • Haploidentical hematopoietic stem cell transplantation (haplo-HSCT) is an effective treatment for blood cancers, but patients often face recurrent infections post-transplant.
  • A study conducted on 19 patients receiving CD45RA-depleted donor lymphocyte infusions (DLI) found that this approach enhances the immune response without increasing risks associated with naïve T-cells.
  • Results showed that specific memory T-cells, particularly those targeting cytomegalovirus (CMV), proliferated significantly and maintained their presence for at least a month post-infusion, suggesting better protection against viral infections.
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Innate lymphoid cells (ILCs) were firstly described by different independent laboratories in 2008 as tissue-resident innate lymphocytes mirroring the phenotype and function of T helper cells. ILCs have been subdivided into three distinct subgroups, ILC1, ILC2 and ILC3, according to their cytokine and transcriptional profiles. Subsequently, also Natural Killer (NK) cells, that are considered the innate counterpart of cytotoxic CD8 T cells, were attributed to ILC1 subfamily, while lymphoid tissue inducer (LTi) cells were attributed to ILC3 subgroup.

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Even with high-dose post-transplant cyclophosphamide (PT-Cy) which was initially introduced for graft-versus-host disease (GvHD) prevention in the setting of HLA-haploidentical transplantation, both acute and chronic GvHDs remain a major clinical challenge. Despite improvements in the understanding of the pathogenesis of both acute and chronic GvHDs, reliable biomarkers that predict their onset have yet to be identified. We recently studied the potential correlation between extracellular vesicles (EVs) and the onset of acute (a)GvHD in transplant recipients from related and unrelated donors.

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Article Synopsis
  • Haploidentical hematopoietic stem cell transplantation (h-HSCT) is an effective treatment for hematologic cancers, but opportunistic viral infections can negatively impact patient outcomes.
  • Recent research shows that human cytomegalovirus (HCMV) plays a role in speeding up the recovery of natural killer (NK) cells post-transplant, with specific NK cell subsets showing increased presence during HCMV infection.
  • The study highlights that these NK cells, while expanding, also exhibit signs of dysfunction due to changes in gene expression and exhaustion markers, affecting their ability to produce key immune signals like IFN-γ, largely influenced by viral interactions.
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Allogeneic stem cell transplantation from haploidentical donor using post-transplantation cyclophosphamide has been used to cure hematological diseases. Because of slow immunological reconstitution, there is an increased incidence of viral infection. The aim of our study was to prospectively evaluate the efficacy and the feasibility of a CD45RA+ depleted donor lymphocytes infusion (DLI) in terms of reduction of viral infection early after haploidentical transplantation.

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Immune checkpoints refer to a plethora of inhibitory pathways of the immune system that play a crucial role in maintaining self-tolerance and in tuning the duration and amplitude of physiological immune responses to minimize collateral tissue damages. The breakdown of this delicate balance leads to pathological conditions, including cancer. Indeed, tumor cells can develop multiple mechanisms to escape from immune system defense, including the activation of immune checkpoint pathways.

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In the context of allogeneic transplant platforms, human leukocyte antigen (HLA)-haploidentical hematopoietic stem cell transplantation (haplo-HSCT) represents one of the latest and most promising curative strategies for patients affected by high-risk hematologic malignancies. Indeed, this platform ensures a suitable stem cell source immediately available for virtually any patents in need. Moreover, the establishment in recipients of a state of immunologic tolerance toward grafted hematopoietic stem cells (HSCs) remarkably improves the clinical outcome of this transplant procedure in terms of overall and disease free survival.

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  • Natural Killer (NK) cells are special immune cells that help the body fight against bad cells like cancer or virus-infected cells by recognizing when they aren't supposed to be there.
  • These NK cells check if other cells have a marker called MHC-I on their surface; if the marker is missing or low, the NK cells are allowed to attack and kill those bad cells.
  • Scientists are studying how a specific receptor named NKG2A helps NK cells mature and work better to attack cancer cells, and they are looking at ways to use this knowledge to create new cancer treatments.
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Natural killer cells are the first lymphocyte population to reconstitute early after non-myeloablative and T cell-replete haploidentical hematopoietic stem cell transplantation with post-transplant infusion of cyclophosphamide. The study herein characterizes the transient and predominant expansion starting from the second week following haploidentical hematopoietic stem cell transplantation of a donor-derived unconventional subset of NKp46/CD56/CD16 natural killer cells expressing remarkably high levels of CD94/NKG2A. Both transcription and phenotypic profiles indicated that unconventional NKp46/CD56/CD16 cells are a distinct natural killer cell subpopulation with features of late stage differentiation, yet retaining proliferative capability and functional plasticity to generate conventional NKp46/CD56/CD16 cells in response to interleukin-15 plus interleukin-18.

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