A5032423973- Immune Cell Function and Interaction
- Immune cells in cancer
- Cancer Immunotherapy and Biomarkers
- CAR-T cell therapy research
- T-cell and B-cell Immunology
- Immunotherapy and Immune Responses
- Chemokine receptors and signaling
- Inflammatory mediators and NSAID effects
- Immune Response and Inflammation
- Pancreatic and Hepatic Oncology Research
- Cytomegalovirus and herpesvirus research
- Extracellular vesicles in disease
- Lymphoma Diagnosis and Treatment
- Cell death mechanisms and regulation
- Phagocytosis and Immune Regulation
- Hematopoietic Stem Cell Transplantation
- Uterine Myomas and Treatments
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Neuroinflammation and Neurodegeneration Mechanisms
- Endometriosis Research and Treatment
- Sex and Gender in Healthcare
- Cancer, Stress, Anesthesia, and Immune Response
- Acute Myeloid Leukemia Research
- Endometrial and Cervical Cancer Treatments
- Advanced Surface Polishing Techniques
Karolinska Institutet
2015-2024
Karolinska University Hospital
2017-2021
University of Minnesota Medical Center
2018-2020
University of Minnesota
2015-2017
Masonic Cancer Center
2017
Cancer Research Center
2015
Gene Therapy Laboratory
2012
Abstract Purpose: Increased frequencies of myeloid-derived suppressor cells (MDSC) correlate with poor prognosis in patients cancers. Tumor-derived prostaglandin-E2 (PGE2) plays an important role inducing MDSCs. However, the detailed mechanisms this induction remain unknown. To develop targeted therapies for MDSCs, we sought to investigate molecular basis PGE2-regulated accumulation MDSCs and their functional consequence on natural killer (NK) cell activity. Experimental Design: The effects...
Human cytomegalovirus (CMV)-induced adaptive natural killer (NK) cells display distinct phenotypic and functional characteristics, including properties of immune memory. We hypothesized that these may be more resistant to suppression mediated by immunoregulatory cell subsets, making them attractive for use in cancer therapy. Here we report relative conventional NK cells, express lower levels the inhibitory receptor T-cell Ig ITIM domain (TIGIT), which results resistance myeloid-derived...
Abstract The progression and metastatic capacity of solid tumors are strongly influenced by immune cells in the tumor microenvironment. In non–small cell lung cancer (NSCLC), accumulation anti-inflammatory tumor-associated macrophages (TAM) is associated with worse clinical outcome resistance to therapy. Here we investigated landscape NSCLC presence protumoral TAMs expressing macrophage receptor collagenous structure (MARCO). MARCO-expressing TAM numbers correlated increased occurrence...
The study of human macrophages and their ontogeny is an important unresolved issue. Here, we use a humanized mouse model expressing cytokines to dissect the development lung from hematopoiesis in vivo. Human CD34+ hematopoietic stem progenitor cells (HSPCs) generated three macrophage populations, occupying separate anatomical niches lung. Intravascular cell labeling, transplantation, fate-mapping studies established that classical CD14+ blood monocytes derived HSPCs migrated into tissue gave...
Maturation of human natural killer (NK) cells as defined by accumulation cell-surface expression CD57 is associated with increased cytotoxic character and TNF IFNγ production upon target-cell recognition. Notably, multiple studies point to a unique role for CD57+ NK in cancer immunosurveillance, yet there scant information about how they mature. In this study, we show that pharmacologic inhibition GSK3 kinase peripheral blood expanded ex vivo IL15 greatly enhances upregulation late-stage...
Significance Here we report that targeting the pattern recognition receptor MARCO on macrophages within tumor alters their polarization and in turn activate natural killer (NK) cells to kill tumor. We describe mechanism of action, including NK are induced use receptor-mediated killing cancer cells. Furthermore, find this type treatment works combination with T cell-targeted checkpoint therapies. then transfer finding humans similar subpopulations human also block Finally, these a new...
Natural killer (NK) cells are capable of fighting viral infections and cancer. However, these responses inhibited by immune suppressor in the tumor microenvironment. Tumor progression promotes recruitment generation intratumoral regulatory T (Treg), associated with a poor prognosis cancer patients. Here, we show that canonical NK highly susceptible to Treg-mediated suppression, contrast resistant CD57
Although metabolic reprogramming within tumor cells and microenvironment (TME) is well described in breast cancer, little known about how the interplay of immune state cancer metabolism evolves during treatment. Here, we characterize immunometabolic profiles tissue samples longitudinally collected from individuals with before, after neoadjuvant chemotherapy (NAC) using proteomics, genomics histopathology. We show that pre-, on-treatment dynamic changes state, proteins cell gene expression...
Abstract Overexpression of the receptor tyrosine kinases HER2 and HER3 is associated with a poor prognosis in several types cancer. Presently, HER2- as well HER3-targeted therapies are clinical practice or evaluated within trials, including treatment mAbs mediating growth inhibition and/or activation Ab-induced innate adaptive cellular immunity. A better understanding how HER2/HER3 signaling tumors influences immune mechanisms therefore warranted. In this study, we demonstrate that regulates...
Doxorubicin (DOX) is an anthracycline antibiotic that widely used to treat different types of malignancy. In this study, it was studied whether DOX could be render tumor cells susceptible apoptosis by NK and T cells. Pretreatment with subapoptotic doses sensitized cell lines various histotypes both resulting in a 3.7 32.7% increase lysis (2.5 mean fold increase, p < 0.0001) 2.9 14.2% (3.0 mean-fold 0.05), respectively. The sensitizing effect the drug primarily dependent on necrosis...
Highlights•NK cells and γδ T reconstitute early after allo-HSCT.•Reconstitution of vδ2+ depends on the stem cell source is less cord blood transplant.•Adaptive NK Vδ1+ are enhanced by CMV reactivation.•Bisphosphonates, IL-15, targeting through CD16 enhance innate immunity allo-HSCT.AbstractRelapse most frequent cause treatment failure allogeneic hematopoietic transplantation (allo-HSCT). Natural killer (NK) allo-HSCT, contribute to tumor immunosurveillance via major histocompatibility...
Altered BM hematopoiesis and immune suppression are hallmarks of myelodysplastic syndrome (MDS). While the microenvironment influences malignant hematopoiesis, mechanism leading to MDS-associated is unknown. We tested whether mesenchymal stromal cells (MSCs) contribute this process. Here, we developed a model study cultured MSCs from patients with MDS (MDS-MSCs) compared those aged-matched normal controls for regulation function. MDS-MSCs healthy donor (HD-MSCs) exhibited similar in vitro...
Immunotherapy for cancer that aims to promote T cell anti-tumor activity has changed current clinical practice, where some previously lethal cancers have now become treatable. However, trials with low response rates been disappointing pancreatic ductal adenocarcinoma (PDAC). One suggested explanation is the accumulation of dominantly immunosuppressive tumor-associated macrophages and myeloid-derived suppressor cells in tumor microenvironment (TME). Using retrospectively collected specimens...
Abstract Adaptive Natural Killer (aNK) cells have emerged as a subset of NK with memory-like properties and specific cytotoxicity, offering promising therapeutic potential in cancer immunotherapy. In this study, we explored the role aNK high-grade serous ovarian (HGSOC), focusing on their ability to establish tumor-specific immune memory effectively target autologous tumors. Through combination silico, vitro, ex vivo approaches, demonstrated that cells, contrast conventional (cNK) exhibit...
Dendritic cell (DC) vaccines induce T‐cell responses in cancer patients. However, there is a paucity of data regarding the role DC shaping natural killer (NK) responses. Here, we observe that NK cells are less activated following vaccination. In vitro, DC‐mediated inhibition did not require cell‐to‐cell contact, but required increased Signal transducer and activator transcription 3 (STAT3) phosphorylation (pSTAT3) DCs. When STAT3 was inhibited DCs, found DCs suppress cells, observed an...
Dendritic cell (DC) vaccines have been demonstrated to elicit immunological responses in numerous cancer immunotherapy trials. However, long-lasting clinical effects are infrequent. We therefore sought establish a protocol generate DC with greater immunostimulatory capacity. Immature were generated from healthy donor monocytes by culturing the presence of IL-4 and GM-CSF further differentiated into mature addition cocktails containing different cytokines toll-like receptor (TLR) agonists....
Sex-driven immune differences can affect tumor progression and the landscape of microenvironment. Deeper understanding these in males females inform patient selection to improve sex-optimized immunotherapy treatments. In this study, single-cell RNA sequencing protein analyses uncovered a subpopulation myeloid cells pancreatic lesions associated with an immune-excluded phenotype effector T-cell exhaustion exclusively females. This was positively correlated poor survival genetic signatures...
Natural killer ( NK ) cells are innate lymphocytes that able to directly kill tumor through different mechanisms including ligation of TNF ‐related apoptosis‐inducing ligand TRAIL receptors. Zoledronic acid ZA is a bisphosphonate known upregulate the expression on human γδ T cells. Here, we investigated whether exposure would and augment their cytotoxicity against When cocultured with monocytes, treatment IL ‐2 resulted in significant upregulation p = 0.002). Consequently, ‐primed were...
Regulatory T cells (Treg) suppress anti-tumor immune responses and their infiltration in the tumor microenvironment is associated with inferior prognosis cancer patients. Thus, order to enhance responses, selective depletion of Treg highly desired. We found that treatment zoledronic acid (ZA) resulted a decrease frequency was significant increase proliferation natural killer (NK) peripheral blood patients metastatic cancer. In vitro, genome-wide transcriptomic analysis revealed alterations...