A5007869818- Immune Cell Function and Interaction
- Cancer Immunotherapy and Biomarkers
- Immunotherapy and Immune Responses
- CAR-T cell therapy research
- Immune cells in cancer
- T-cell and B-cell Immunology
- Myeloproliferative Neoplasms: Diagnosis and Treatment
- Cancer Research and Treatments
- vaccines and immunoinformatics approaches
- Lymphoma Diagnosis and Treatment
- Multiple Myeloma Research and Treatments
- Chronic Myeloid Leukemia Treatments
- Eosinophilic Disorders and Syndromes
- Tryptophan and brain disorders
- Monoclonal and Polyclonal Antibodies Research
- Adenosine and Purinergic Signaling
- Neuroinflammation and Neurodegeneration Mechanisms
- Chemokine receptors and signaling
- Curcumin's Biomedical Applications
- Macrophage Migration Inhibitory Factor
- Cancer, Stress, Anesthesia, and Immune Response
- Sexual Differentiation and Disorders
- Advanced Nanomaterials in Catalysis
- FOXO transcription factor regulation
- Tannin, Tannase and Anticancer Activities
Herlev Hospital
2014-2025
Copenhagen University Hospital
2012-2024
Bahauddin Zakariya University
2024
University of Copenhagen
2015-2022
Gentofte Hospital
2016
Government Medical College
2007
Arginase-1 (Arg1) expressing tumor-associated macrophages (TAMs) may create an immune-suppressive tumor microenvironment (TME), which is a significant challenge for cancer immunotherapy. We previously reported the existence of Arg1-specific memory T cells among peripheral blood mononuclear (PBMCs) and described that Arg-1-based immune modulatory vaccines (IMVs) control growth alter M1/M2 macrophage ratio in murine models cancer. In present study, we investigated how can directly target TAMs...
In the absence of a local inflammatory response, expression MHC class II molecules is restricted mainly to hematopoietic cells and thymus epithelium. However, certain tumors, such as melanoma, may acquire aberrant constitutive II. set primary melanoma cell populations correspondingly expanded autologous tumor-infiltrating lymphocytes (TIL), we show how on associates with strong II-restricted CD4(+) T-cell responses that are specific for tumors. Notably, found tumor-specific were dominated by...
PD-L1 (CD274) contributes to functional exhaustion of T cells and limits immune responses in patients with cancer. In this study, we report the identification an human leukocyte antigen (HLA)-A2-restricted epitope from PD-L1, describe natural, cytolytic T-cell reactivity against peripheral blood cancer healthy individuals. Notably, PD-L1-specific were able not only recognize kill tumor but also PD-L1-expressing dendritic a PD-L1-dependent manner, insofar as ablation rescued killing....
Tumor cells and tumor-infiltrating macrophages produce the chemokine CCL22, which attracts regulatory T (Tregs) into tumor microenvironment, decreasing anticancer immunity. Here, we investigated possibility of targeting CCL22-expressing by activating specific cells. We analyzed CCL22 protein signal sequence, identifying a human leukocyte antigen A2- (HLA-A2-) restricted peptide epitope, then used to stimulate peripheral blood mononuclear (PMBCs) expand populations CCL22-specific in vitro....
Programmed cell death 1 ligand (PD-L1) is an important regulator of T-cell responses and may consequently limit anticancer immunity. We have recently identified PD-L1-specific, cytotoxic CD8+ T cells. In the present study, we develop these findings report that CD4+ helper cells spontaneously recognize PD-L1. examined locality a previously HLA-A*0201-restricted PD-L1-epitope for presence possible epitopes. Thus, naturally occurring PD-L1-specific among peripheral blood lymphocytes cancer...
Abstract Cancer immunotherapy can result in durable tumor regressions some patients. However, patients who initially respond often experience progression. Here, we report mechanistic evidence of tumoral immune escape an exemplary clinical case: a patient with metastatic melanoma developed disease recurrence following initial, unequivocal radiologic complete regression after T-cell–based immunotherapy. Functional cytotoxic T-cell responses, including responses to one mutant neoantigen, were...
Background The enzyme indoleamine 2,3-dioxygenase (IDO) contributes to immune tolerance in a variety of settings. In cancer IDO is expressed within the tumor itself as well antigen-presenting cells tumor-draining lymph nodes, where it endorses establishment peripheral antigens. Recently, we described cytotoxic CD8+ T-cell reactivity towards IDO-derived peptides. Methods and Findings present study, show that CD4+ helper T additionally spontaneously recognize IDO. Hence, scrutinized vicinity...
Cell surface molecules of the B7/CD28 family play an important role in T-cell activation and tolerance. The relevance PD-1/PD-L1 pathway cancer has been extensively studied whereas PD-L2 received less attention. However, recently expression was described to be independently associated with clinical response anti-PD1-treated patients. Here, we investigated whether might represent a natural target that induces specific T cells. We identified spontaneous reactivity against two epitopes located...
The enzyme arginase-1 reduces the availability of arginine to tumor-infiltrating immune cells, thus reducing T-cell functionality in tumor milieu. Arginase-1 is expressed by some cancer cells and inhibitory such as myeloid-derived suppressor (MDSCs) tumor-associated macrophages (TAMs), its expression associated with poor prognosis. In present study, we divided protein sequence into overlapping 20-amino-acid-long peptides, generating a library 31 peptides covering whole sequence. Reactivity...
We recently described naturally occurring PD-L1-specific T cells that recognize PD-L1-expressing immune as well malignant cells. In the present study, we investigated whether immunogenicity of a dendritic cell (DC)-based vaccine could be influenced by co-stimulation with known PD-L1-derived epitope. incubated peptide epitope (19 amino acids long) or control (an irrelevant HIV epitope) peripheral blood mononuclear from patients melanoma who had received DC-based vaccine. observed...
Abstract Mutations in exon 9 of the calreticulin gene ( CALR ) frequently occur patients with chronic myeloproliferative neoplasms (MPN). Patients exhibit spontaneous cellular immune responses to epitopes derived from mutant C-terminus, and -mutant-specific T cells recognize autologous -mutant malignant cells. This study investigated whether naturally wt MPN-patients healthy individuals. Specific against peptide sequence were detected both Healthy donors displayed more frequent stronger...
Staphylococcus aureus and its toxins have been linked to disease progression mortality in advanced stages of cutaneous T-cell lymphoma (CTCL). CD8+ T cells play a crucial role anti-cancer responses high cell numbers tumor lesions are associated with favorable prognosis CTCL. Here, we show that from both healthy donors Sézary syndrome patients highly susceptible death induced by Staphylococcal alpha-toxin, whereas malignant not. Importantly, alpha-toxin almost completely blocks cytotoxic...
Arginase-1 (Arg1) is expressed by regulatory myeloid cells in the tumor microenvironment (TME), where they play a pro-tumorigenic and T-cell suppressive role. Arg1-specific CD4+ CD8+ memory T have been observed both healthy individuals cancer patients. However, while function of anti-regulatory has characterized, our knowledge only scarce. In current study, we describe immune-modulatory capabilities cells. We generated cell clones to target Arg1-expressing Our results demonstrate that these...
Immune checkpoint blockade with monoclonal antibodies targeting programmed death 1 (PD-1) and its ligand PD-L1 has played a major role in the rise of cancer immune therapy. We have identified naturally occurring self-reactive T cells specific to both healthy donors patients. Stimulation peptide (IO103), activates these exhibit inflammatory anti-regulatory functions that include cytotoxicity against PD-L1-expressing target cells. This prompted initiation present first-in-human study...
Tryptophan-2,3-dioxygenase (TDO) physiologically regulates systemic tryptophan levels in the liver. However, numerous studies have linked cancer with activation of local and metabolism. Indeed, similar to other heme dioxygenases TDO is constitutively expressed many cancers. In present study, we detected presence both CD8