Search results for "Unity"
showing 10 items of 3852 documents
Immunologic microenvironment and personalized treatment in multiple myeloma.
2013
Introduction: Multiple myeloma (MM) is characterized by generalized immune suppression and increased susceptibility to infections and secondary malignancies. Malignant plasma cells (PCs) modulate the bone marrow microenvironment to favor their own survival and proliferation. These events lead to a severe deregulation of immune effectors. Extensive studies have been conducted to unveil the mechanisms through which MM cells negatively modulate immunity and to develop therapeutical approaches for restoring an efficient anti-MM immune response. Areas covered: This review article covers both the immunosuppressive effects exerted by MM and the immunomodulatory potential of novel anti-MM agents. A…
Vaccination with ENO1 DNA Prolongs Survival of Genetically Engineered Mice with Pancreatic Cancer
2013
Background & Aims Pancreatic ductal adenocarcinoma (PDA) is an aggressive tumor, and patients typically present with late-stage disease; rates of 5-year survival after pancreaticoduodenectomy are low. Antibodies against α-enolase (ENO1), a glycolytic enzyme, are detected in more than 60% of patients with PDA, and ENO1-specific T cells inhibit the growth of human pancreatic xenograft tumors in mice. We investigated whether an ENO1 DNA vaccine elicits antitumor immune responses and prolongs survival of mice that spontaneously develop autochthonous, lethal pancreatic carcinomas. Methods We injected and electroporated a plasmid encoding ENO1 (or a control plasmid) into Kras G12D /Cre (KC) mice …
Bortezomib Induces Anti–Multiple Myeloma Immune Response Mediated by cGAS/STING Pathway Activation
2021
Abstract The proteasome inhibitor bortezomib induces apoptosis in multiple myeloma cells and has transformed patient outcome. Using in vitro as well as in vivo immunodeficient and immunocompetent murine multiple myeloma models, we here show that bortezomib also triggers immunogenic cell death (ICD), characterized by exposure of calreticulin on dying multiple myeloma cells, phagocytosis of tumor cells by dendritic cells, and induction of multiple myeloma–specific immunity. We identify a bortezomib-triggered specific ICD gene signature associated with better outcome in two independent cohorts of patients with multiple myeloma. Importantly, bortezomib stimulates multiple myeloma cell immunogen…
POLYPHENOLS FROM RED WINE MODULATE IMMUNE RESPONSIVENESS: BIOLOGICAL AND CLINICAL SIGNIFICANCE.
2008
Many studies have been conducted on the effects of red wine polyphenols on certain diseases, primarily, coronary heart disease (CHD) and, in this respect, evidence has been demonstrated that intake of red wine is associated with a reduction of CHD symptomatology. In this framework, the purpose of this review is to illustrate the effects of polyphenols on immune cells from human healthy peripheral blood. Data will show that polyphenols are able to stimulate both innate and adaptive immune responses. In particular, the release of cytokines such as interleukin (IL)-12, interferon (IFN)-gamma, and IL-10 as well as immunoglobulins may be important for host protection in different immune related …
Transcription factors controlling development and function of innate lymphoid cells.
2014
Abstract Innate lymphoid cells (ILCs) are a heterogeneous group of lymphocytes, which play an important role in tissue homeostasis at epithelial surfaces. They are scarce in spleen and lymph nodes, but substantial numbers can be found in the intestinal mucosa even at steady state. There, they represent the first line of defence against invading pathogens and contribute to lymphorganogenesis, tissue repair and, when inappropriately activated, immune pathology. Lineage-specific development, function and maintenance of these cells depend on a restricted set of transcription factors that partially emerged as a result of diversification and selection during vertebrate evolution. The differential…
Dynamics of gut mucosal and systemic Th1/Th2 cytokine responses in interferon-gamma and interleukin-12p40 knock out mice during primary and challenge…
2009
Cryptosporidium parvum is an intracellular parasite causing enteritis which can become life-threatening in the immunocompromised host. CD4+ T cells and interferon (IFN)-gamma play dominant roles in host immune response to infection. However, effector mechanisms that are responsible for recovery from infection are poorly understood. In the present study we analyzed mice deficient in IFN-gamma or interleukin (IL)-12 in parallel to C57BL/6 wild type mice as models for murine cryptosporidiosis. Our results identified IFN-gamma as the key cytokine in the innate as well as adaptive immunity during primary and also challenge C. parvum infection. Furthermore, both Th1 and Th2 cytokines appear to co…
Irregular Cytokine Pattern of CD4+T Lymphocytes in Response toStaphylococcus aureusin Patients with Wegener's Granulomatosis
1999
The initial stage of Wegener's Granulomatosis (WG) is often marked by symptoms of infection and it has been postulated that a bacterial infection could be the aetiologic factor of this disease. The objective of our work was to investigate T-cell-mediated immunity in WG by testing proliferative responses on bacterial antigens and particularly Staphylococcus aureus. We investigated the bulk proliferative response of peripheral blood lymphocytes (PBL) from patients with clinically active WG to gram-positive bacteria and purified proteinase 3 (PR-3), the major target antigen of c-ANCA. We generated S. aureus-specific PBL-derived T-cell lines and T-cell clones (TLC). In two WG patients 27 TLC we…
Cytokine components and mucosal immunity in the oviduct of Xenopus laevis (amphibia, pipidae)
2011
Abstract Most studies on the mucosal immunity in female reproductive tissues have been performed in mammals. In all species, apart from their reproductive strategies, immunity in the genital mucosa is required to defend the host against luminal pathogens. In this study we investigated the role of the innate immunity of the oviductal mucosa of Xenopus laevis , an amphibian characterized by external fertilization. In particular we examined the expression and localization of Interleukin-1β (IL1B), Macrophage migration inhibitory factor (MIF) and Interleukin-1 receptor type 1 (IL1R1) in different oviductal portions including an upper glandular region, an intermediate and a lower aglandular regi…
A Role for Leukocyte-Derived IL-1RA in DC Homeostasis Revealed by Increased Susceptibility of IL-1RA-Deficient Mice to Cutaneous Leishmaniasis
2011
Dendritic cell (DC)-derived IL-1α/β plays a critical role in the induction of T helper type 1 (Th1)-dependent immunity against Leishmania . DCs from susceptible BALB/c mice produce less IL-1α/β when compared with resistant C57BL/6 mice, contributing to aberrant Th2 development and ultimate death of infected mice. We have extended our studies of the role of IL-1 in leishmaniasis using IL-1RA -/- BALB/c mice that are characterized by upregulated IL-1 receptor signaling. Unexpectedly, infection of IL-1RA -/- mice led to significantly worsened disease outcome with larger lesions, dramatically higher parasite burdens, and decreased IFN-γ production by antigen-specific T cells. We determined that…
IL-1 signalling is dispensable for protective immunity in Leishmania-resistant mice
2010
Leishmaniasis is a parasitic disease affecting ∼12 million people. Control of infection (e.g. in C57BL/6 mice) results from IL-12-dependent production of IFNγ by Th1/Tc1 cells. In contrast, BALB/c mice succumb to infection because of preferential Th2-type cytokine induction. Infected dendritic cells (DC) represent important sources of IL-12. Genetically determined differences in DC IL-1α/β production contribute to disease outcome. Whereas the course of disease was not dramatically altered in IL-1RI(-/-) mice, local administration of IL-1α to infected C57BL/6 mice improved disease outcome. To definitively elucidate the involvement of IL-1 in immunity against leishmaniasis, we now utilized IL…