A5020355212- Cancer Immunotherapy and Biomarkers
- Immune cells in cancer
- Immune Cell Function and Interaction
- Immunotherapy and Immune Responses
- Cancer Research and Treatments
- Psoriasis: Treatment and Pathogenesis
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Inflammatory Bowel Disease
- Cancer Cells and Metastasis
- Inflammatory Biomarkers in Disease Prognosis
- T-cell and B-cell Immunology
- Cytokine Signaling Pathways and Interactions
- CAR-T cell therapy research
- Mesenchymal stem cell research
- 3D Printing in Biomedical Research
- Monoclonal and Polyclonal Antibodies Research
- Immune Response and Inflammation
- Chemokine receptors and signaling
- Virus-based gene therapy research
- vaccines and immunoinformatics approaches
- Oral and Maxillofacial Pathology
- Mycobacterium research and diagnosis
- Gut microbiota and health
- Atherosclerosis and Cardiovascular Diseases
- Platelet Disorders and Treatments
Immunocore (United Kingdom)
2022-2023
University of Basel
2011-2020
University Hospital of Basel
2013-2018
See-Spital
2017
Shanghai East Hospital
2014
Kantonsschule Olten
2014
Kantonsspital St. Gallen
2014
Ospedale San Giovanni Bellinzona
2014
Ospedale regionale di Lugano
2014
National Research Council
2014
Objective Tumour-infiltrating lymphocytes (TILs) favour survival in human colorectal cancer (CRC). Chemotactic factors underlying their recruitment remain undefined. We investigated chemokines attracting T cells into CRCs, cellular sources and microenvironmental triggers. Design Expression of genes encoding immune cell markers, bacterial 16S ribosomal RNA (16SrRNA) was assessed by quantitative reverse transcription-PCR fresh CRC samples corresponding tumour-free tissues. Chemokine receptor...
Abstract Purpose: Tumor infiltration by different T lymphocyte subsets is known to be associated with favorable prognosis in colorectal cancer. Still debated the role of innate immune system. We investigated clinical relevance, phenotypes, and functional features cancer–infiltrating CD66b+ neutrophils their crosstalk CD8+ cells. Experimental Design: cell was analyzed IHC on a tissue microarray including >650 evaluable cancer samples. Phenotypic profiles tissue-infiltrating peripheral...
The immune contexture predicts prognosis in human colorectal cancer (CRC). Whereas tumour-infiltrating CD8+ T cells and myeloid CD16+ myeloperoxidase (MPO)+ are associated with favourable clinical outcome, interleukin (IL)-17-producing have been reported to correlate severe prognosis. However, their phenotypes functions continue be debated.To investigate relevance, functional features of CRC-infiltrating, IL-17-producing cells.IL-17 staining was performed by immunohistochemistry on a tissue...
Background Colorectal cancer (CRC) infiltration by adaptive immune system cells correlates with favorable prognosis. The role of the innate is still debated. Here we addressed prognostic impact CRC neutrophil granulocytes (NG). Methods A TMA including healthy mucosa and clinically annotated specimens (n = 1491) was stained MPO CD15 specific antibodies. MPO+ CD15+ positive were counted three independent observers. Phenotypic profiles infiltrating validated flow cytometry on cell suspensions...
Summary Accumulating evidence suggests an immune-modulatory role for platelets (PLT) and PLT-derived microvesicles. In particular, ectosomes, i.e. vesicles budding from PLT surface, have been shown to exert immunosuppressive activities on phagocytes. Here we investigated the effects mediated by ectosomes (PLT-Ecto) CD4+ T cells. Exposure of activated cells PLT-Ecto decreased their release IFNγ, TNFα IL-6, increased production TGF-β1. Concomitantly, PLT-Ecto-exposed displayed frequencies...
Colorectal cancer infiltration by CD16(+) myeloid cells correlates with improved prognosis. We addressed mechanistic clues and gene protein expression of cytokines potentially associated macrophage polarization.GM-CSF or M-CSF-stimulated peripheral blood CD14(+) from healthy donors were cocultured colorectal cells. Tumor cell proliferation was assessed (3)H-thymidine incorporation. Expression cytokine genes in autologous mucosa tested quantitative, real-time PCR. A tumor microarray (TMA)...
Platelet (PLT) transfusions are potentially life saving for individuals with low PLT numbers; however, previous work revealed that associated increased infection risk. During storage, intended transfusion continuously shed ectosomes (Ecto) from their surface, which express immunomodulatory molecules like phosphatidylserine or TGF-β1. Recently, PLT-Ecto were shown to reduce proinflammatory cytokine release by macrophages and favor the differentiation of naive T cells toward regulatory cells....
Mesenchymal stem/stromal cells (MSC) are multipotent precursors endowed with the ability to home primary and metastatic tumor sites, where they can integrate into tumor-associated stroma. However, molecular mechanisms outcome of their interaction cancer have not been fully clarified. In this study, we investigated effects mediated by bone marrow-derived MSC on human colorectal (CRC) in vitro vivo. We found that triggered epithelial-to-mesenchymal transition (EMT) vitro, as indicated...
// Benjamin Weixler 1 , Eleonora Cremonesi 2 Roberto Sorge 3 Manuele Giuseppe Muraro Tarik Delko Christian A. Nebiker Silvio Däster Valeria Governa Francesca Amicarella Savas D. Soysal 1,2 Christoph Kettelhack Urs W. von Holzen 1,4 Serenella Eppenberger-Castori 5 Giulio C. Spagnoli Daniel Oertli Giandomenica Iezzi Luigi Terracciano Tornillo Sconocchia 6,* and Raoul Droeser 1,2,* Department of Surgery, University Hospital Basel, Switzerland Institute Surgical Research Management (ICFS)...
Abstract Immune cell infiltration in colorectal cancer effectively predicts clinical outcome. IL22, produced by immune cells, plays an important role inflammatory bowel disease, but its relevance remains unclear. Here, we addressed the prognostic significance of IL22+ and effects on composition tumor microenvironment. Tissue microarrays (TMA) were stained with IL22-specific mAb, positive cells counted expert pathologists. Results correlated clinicopathologic data overall survival (OS)....
Abstract T-cell-engaging bispecifics have great clinical potential for the treatment of cancer and infectious diseases. The binding affinity kinetics a bispecific molecule both target T-cell CD3 substantial effects on potency specificity, but rules governing these relationships are not fully understood. Using immune mobilizing monoclonal TCRs against (ImmTAC) molecules as model, we explored impact altering specificity redirected response. This class binds specific peptides presented by human...
Colorectal cancer (CRC) infiltration by cells expressing myeloperoxidase (MPO) or CD8 positive T lymphocytes has been shown to be independently associated with favorable prognosis. We explored the relationship occurring between CD8+ and MPO+ cell CRC infiltration, its impact on clinical-pathological features prognostic significance in a tissue microarray (TMA) including 1,162 CRC. observed that showing high are characterized prognosis as of cancers infiltration. However, infiltrating did not...
Immunotherapy has emerged during the past two decades as an innovative and successful form of cancer treatment. However, frequently, mechanisms actions are still unclear, predictive markers insufficiently characterized, preclinical assays for treatments poorly reliable. In this context, analysis tumor/immune system interaction plays key roles, but may be unreliably mirrored by in vivo experimental models standard bidimensional culture systems. Tridimensional cultures tumor cells have been...
Aims . A trend towards local excision of early rectal cancers has prompted us to investigate if immunoprofiling might help in predicting lymph node involvement this subgroup. Methods tissue microarray 126 biopsies cancer (T1 and T2) was stained for several immunomarkers the innate adaptive immune response. Patients’ survival nodal status were analyzed correlated with infiltration different cells. Results Of all tested markers, only CD8 (<mml:math...
Abstract Background and aims: Evidence from experimental models suggests that IL-17 T helper (Th)-17 cells may contribute to anti-tumor immune responses. The role played by in human cancers remains however, be clarified. We have investigated phenotypes prognostic significance of IL-17-producing IL-17-responsive colorectal cancer (CRC). Methods: Expression receptors (IL-17R) A C was on freshly isolated CRC specimens flow cytometry, combination with surface molecules identifying specific cell...
Abstract Introduction: Colorectal cancer (CRC) is a leading cause of cancer-related death. CRC infiltration by immune cells, including cytotoxic CD8+ T cells (CTLs), IFN-gamma-producing T-helper 1 (Th1), Foxp3+ regulatory (Tregs) and CD16+ MPO+ neutrophils, associated with favorable prognosis. However, chemokines driving these cell populations into the tumor site, their cellular sources microenvironmental triggers remain to be elucidated. Aim: We investigated chemokine/chemokine receptor...
Abstract Colorectal cancer (CRC) is a leading cause of related death. Several studies have convincingly showed that CRC infiltration by immunocompetent cells and, in particular, cytotoxic CD8+ T cells, IFN-γ-producing Foxp3+ regulatory and CD16+ MPO+ neutrophils, significantly associated with prolonged patient survival. However, the factors driving these cell populations into tumor site remain to be elucidated. We are investigating chemokine/chemokine receptor network promoting immune...
Abstract Colorectal cancer (CRC) is a leading cause of cancer-related death. CRC infiltration by immune cells, including cytotoxic CD8+ T cells (CTLs), IFN-gamma-producing T-helper 1 (Th1), Foxp3+ regulatory (Tregs) and CD16+ MPO+ neutrophils, associated with favorable prognosis. However, chemokines driving these cell populations into the tumor site, their cellular sources microenvironmental triggers remain to be elucidated. We investigated chemokine/chemokine receptor network promoting...
Abstract The development of novel three-dimensional (3D) culture systems allowing the survival/expansion primary tumors in vitro may help to bridge gap between conventional bi-dimensional (2D) cultures and animal models, poorly predictive therapeutic responses. We have investigated suitability a previously developed perfused bioreactor system for human tumor tissues. Surgical specimens colorectal cancer (CRC, n = 15), glioblastoma (n 3), breast sarcoma 2), melanoma 1) were used. Tumor...
Abstract Background: Lymphocytic infiltration is known to be associated with a favourable prognosis in human colorectal cancer (CRC). In particular, the presence of CD8+ T cells and, unexpectedly, Foxp3+ regulatory cells, has been found improved patient survival. Recent evidence suggests that IL-17 and helper (Th) 17 might also have an impact on anti-tumour immune responses. We investigated prevalence, phenotype prognostic significance IL-17-producing CRC. Material Methods: expression was...
Abstract Mesenchymal stem/stromal cells (MSC) are multipotent precursors endowed with the ability to home primary and metastatic tumor site. Because of this feature, they currently being used in preclinical models clinical trials as potential vehicles for delivery targeted anti-cancer therapies. Clinical applications MSC however, require a deeper understanding their biology and, particular, interaction cancer cells. In study we have investigated effects mediated by human bone marrow-derived...
<p>CD8+/PBN cross-talk is contact dependent. (A) Cumulative flow-cytometry histograms documenting CD69 expression in CD8+ T cells activated by using different concentrations of surface bound anti-CD3 (TR66, 0.5 and 2μg/ml) soluble anti CD28 (1μg/ml) upon overnight co-culture the presence or absence neutrophils. (B) Representative dot plots showing peripheral blood stimulated suboptimal anti-CD3/ anti-CD28 autologous PBN control transwell conditions, preventing cell-cell contact. (C)...