A5073641806- Immunotherapy and Immune Responses
- HIV Research and Treatment
- Immune Cell Function and Interaction
- T-cell and B-cell Immunology
- Cancer Immunotherapy and Biomarkers
- Monoclonal and Polyclonal Antibodies Research
- vaccines and immunoinformatics approaches
- Mesenchymal stem cell research
- Immune cells in cancer
- Bladder and Urothelial Cancer Treatments
- Osteoarthritis Treatment and Mechanisms
- Cell Adhesion Molecules Research
- HER2/EGFR in Cancer Research
- COVID-19 Clinical Research Studies
- Urinary Tract Infections Management
- Hepatitis C virus research
- Long-Term Effects of COVID-19
- Cytomegalovirus and herpesvirus research
- Immune Response and Inflammation
- Urinary Bladder and Prostate Research
- HIV/AIDS Research and Interventions
- HIV/AIDS drug development and treatment
- Radiopharmaceutical Chemistry and Applications
- Hepatitis B Virus Studies
- Chemokine receptors and signaling
Science for Life Laboratory
2024
Uppsala University
2019-2024
Karolinska Institutet
2013-2019
The demand for controlling T cell responses via dendritic (DC) vaccines initiated a quest reliable and feasible DC modulatory strategies that would facilitate cytotoxicity against tumors or tolerance in autoimmunity. We studied endogenous mechanisms developing monocyte-derived DCs (MoDCs) can induce inflammatory suppressor programs during differentiation, we identified powerful autocrine pathway that, concentration-dependent manner, strongly interferes with differentiation. MoDCs at low...
During the current COVID-19 pandemic, a need for evaluation of already available drugs treatment disease is crucial. Hereby, based on literature review from pandemic and previous outbreaks with corona viruses we analyze impact virus infection cell stress responses redox balance. High levels mortality are noticed in elderly individuals infected SARS-CoV2 during SARS-CoV1 outbreak. Elderly maintain chronic low level inflammation which associated oxidative inflammatory cytokine production,...
Early initiation of antiretroviral therapy (ART) is becoming a common clinical practice according to current guidelines recommending treatment all HIV-1-infected patients. However, it not known whether ART initiated during the early phase infection prevents establishment abnormal phenotypic features previously reported in CD4+ and CD8+T cells chronic HIV-1 infection. In this cross-sectional study, blood specimens were obtained from 17 patients who began shortly after (early [EA]),...
Recent guidelines recommend antiretroviral therapy (ART) to be administered as early possible during HIV-1 infection. Few studies addressed the immunological benefit of commencing ART acute phase We used mass cytometry characterize blood CD4+ T cells from HIV-1–infected patients who initiated or chronic Using this method, we analyzed a large number markers on millions individual immune cells. The results revealed that cell clusters with high expression CD27, CD28, CD127, and CD44, whose...
We observed a cell concentration-dependent differentiation switch among cultured dendritic cells (DCs) triggered by lactic acid, product of glycolytic metabolism. In particular, while interleukin (IL)-12, IL-23, and tumor necrosis factor α (TNFα)-producing, migratory DCs developed in sparse cultures, IL-10-producing, non-migratory differentiated dense cultures. This points to novel opportunity for tailoring DC-based anticancer therapies through metabolism modulation developing DCs.
IL-7 was previously shown to upregulate the expression of molecules important for interaction CD4+ T cells with B cells. It is poorly studied whether has a role in biology follicular helper (Tfh) and if dysregulates B-cell costimulatory on Tfh We review literature provide arguments favor being involved human The CD127 receptor expressed circulating non-Tfh we show that IL-7, but not IL-6 or IL-21, upregulates CD70 PD-1 these conclude cytokine which level elevated during HIV-1 infection, may...
Follicular dendritic cells (FDCs) are important components in the organization of germinal centers lymphoid tissue where, following antigen presentation, B differentiate into memory cells. The possibility establishing primary cell lines from FDCs isolated paved way for characterization FDC biological properties. We exposed to HIV-1 strains vitro and studied changes chemo-attractive properties release inflammatory cytokines.FDC expressed several known putative receptors; viral genome was...
Successful vaccinations rely on antibody responses. Chemokine receptors play an important role in B cell homing to differentiation niches. We assessed CXCR4, CXCR5 and CCR6 expression cells during HIV-1 infection relate it responses against a HBV vaccine. Blood was obtained from 54 healthy controls 38 ART-treated infected children, aviremic (n = 25) or viremic 13). Frequency of naïve memory subsets studied by immunostaining. Homing capacity blood lymphoid inflamed tissues evaluated through...
CD70 molecules expressed by activated T cells provide potent B cell stimulatory signals. We hypothesized that an altered expression might contribute to abnormalities during HIV-1 infection.CD70 and the functional migratory properties of CD4CD70 lymphocytes were analyzed in HIV-1-infected patients humanized mice. Correlations tested between features B-cell activation, apoptosis sensitivity exhaustion.CD4CD70 cohorts CD4 T-cell lymphopenic, viremic or nonlymphopenic, nonviremic noninfected...
Abstract We have previously shown that human monocyte-derived dendritic cells (DCs) acquired different characteristics in dense or sparse cell cultures. Sparsity promoted the development of IL-12 producing migratory DCs, whereas cultures increased IL-10 production. Here we analysed whether density-dependent endogenous breaks could modulate DC-based vaccines. Using murine bone marrow-derived DC models show were essential to achieve several key functions required for immunogenic vaccines,...
The aim of this study was to assess the potential use a selective small molecule MALT1 inhibitor in solid tumor treatment as an immunotherapy targeting regulatory T-cells (Tregs). In vitro, inhibition suppressed proteolytic cleavage MALT1-substrate HOIL1 and blocked IL-2 secretion Jurkat cells. It selectively proliferation PBMC-derived Tregs, with no effect on conventional CD4+ T-cells. vivo, however, evident anti-tumor achieved by monotherapy or combination anti-CTLA4 MB49 cancer model....
Abstract Synthetic peptides are explored in the clinic cancer vaccine development for purpose of inducing tumor-directed T cell responses. Their immunogenicity is dependent on chosen adjuvant and target organ exposure (lymphoid organs). To improve peptide immunogenicity, we have developed a technology enabling cross-linking endogenous, pre-existing circulating antibodies (Abs) by employing three-dimensional chemistry design. Multiple identical tetanus toxin-derived B epitopes (MTTEs)...
Dendritic cells (DCs) are potent antigen presenting that might play contradictory roles during HIV-1 infection, contributing to anti-viral immunity but also viral dissemination and immune evasion. Although DCs characterized by enormous functional diversity, it has not been analyzed how differentially programmed interact with HIV-1. We have previously described the reprogramming of DC development endogenously produced lactic acid accumulated in a cell culture density dependent manner provided...
During anti-retroviral therapy (ART) HIV-1 persists in cellular reservoirs, mostly represented by CD4+ memory T cells. Several approaches are currently being undertaken to develop a cure for infection through elimination (or reduction) of these reservoirs. Few studies have so far been conducted assess the possibility reducing size reservoirs vaccination virologically controlled infected children. We recently study with combined Hepatitis A virus (HAV) and B Virus (HBV) vaccine 22 assessed...
Abstract The mouse bladder 49 (MB49) syngeneic tumors respond to various immunotherapies, both stimulatory immunotherapies and check-point blockers; when are cured it is often an anti-tumor memory response established (previous publications by our group others). Herein we present data suggesting that bladders of orthotopic MB49 tumor bearing mice hold a reservoir lymphocytes surrounding the tumor, wherein they migrate rapidly upon immune adjuvant stimulation. appear form accessible...
The mouse bladder 49 (MB49) syngeneic tumors respond to various immunotherapies, both stimulatory immunotherapies and check-point blockers; when are cured it is often an anti-tumor memory response established (previous publications by our group others). Herein we present data suggesting that bladders of orthotopic MB49 tumor bearing mice hold a reservoir lymphocytes surrounding the tumor, wherein they migrate rapidly upon immune adjuvant stimulation. appear form accessible microenvironment...
Abstract Vaccines based on synthetic long peptides, targeting immunogenic region(s) of tumor associated proteins, are becoming increasingly used in oncology. Synthetic peptides require endogenous processing by antigen presenting cells to be presented T cells, thus reducing the risk presentation non-professional lacking co-stimulation receptors. The formulation and delivery strategies further development as degrade rapidly vivo. Herein we make use a novel adjuvant strategy deliver cells....