A5027677462- Cancer Immunotherapy and Biomarkers
- Gastric Cancer Management and Outcomes
- Esophageal Cancer Research and Treatment
- Colorectal Cancer Treatments and Studies
- HER2/EGFR in Cancer Research
- Pancreatic and Hepatic Oncology Research
- Cancer Genomics and Diagnostics
- Immunotherapy and Immune Responses
- Monoclonal and Polyclonal Antibodies Research
- Glycosylation and Glycoproteins Research
- Cancer Cells and Metastasis
- Gastrointestinal Tumor Research and Treatment
- Cancer Treatment and Pharmacology
- Gut microbiota and health
- CAR-T cell therapy research
- Genetic factors in colorectal cancer
- Cancer, Stress, Anesthesia, and Immune Response
- Liver Diseases and Immunity
- Lung Cancer Treatments and Mutations
- Cytokine Signaling Pathways and Interactions
- Neutropenia and Cancer Infections
- PARP inhibition in cancer therapy
- Hepatocellular Carcinoma Treatment and Prognosis
- Liver Disease Diagnosis and Treatment
- T-cell and B-cell Immunology
Universität Hamburg
2016-2025
University Medical Center Hamburg-Eppendorf
2016-2025
University Cancer Center Hamburg
2020-2024
Martini-Klinik
2021
Klinik und Poliklinik für Neurologie
2016
Pancreatic ductal adenocarcinoma (PDAC) is expected to be the second most deadly cancer by 2040, owing high incidence of metastatic disease and limited responses treatment1,2. Less than half all patients respond primary treatment for PDAC, chemotherapy3,4, genetic alterations alone cannot explain this5. Diet an environmental factor that can influence response therapies, but its role in PDAC unclear. Here, using shotgun metagenomic sequencing metabolomic screening, we show microbiota-derived...
<h3>Importance</h3> In metastatic esophagogastric adenocarcinoma (EGA), the addition of programmed cell death 1 (PD-1) inhibitors to chemotherapy has improved outcomes in selected patient populations. <h3>Objective</h3> To investigate efficacy trastuzumab and PD-1 with cytotoxic T-lymphocyte–associated antigen 4 (CTLA-4) or FOLFOX first-line treatment advanced<i>ERBB2</i>-positive EGA. <h3>Design, Setting, Participants</h3> This phase 2 multicenter, outpatient, randomized clinical trial...
Background In patients with microsatellite stable (MSS) metastatic colorectal cancer (mCRC), immune checkpoint blockade is ineffective, and combinatorial approaches enhancing immunogenicity need exploration. Methods We treated 43 predominantly RAS/BRAF wild-type mCRC on a phase II trial combining chemotherapy the epidermal growth factor receptor antibody cetuximab programmed cell death ligand 1 (PD-L1) avelumab. performed next-generation gene panel sequencing for mutational typing of tumors...
Abstract Background KRAS circulating tumor DNA (ctDNA) has shown biomarker potential for pancreatic ductal adenocarcinoma (PDAC) but not been applied in clinical routine yet. We aim to improve applicability of ctDNA detection PDAC and study the impact blood-draw site time point on detectability prognostic role mutations. Methods 221 blood samples from 108 patients (65 curative, 43 palliative) were analyzed. Baseline peripheral tumor-draining portal venous (PV), postoperative, follow-up...
Skin-migratory dendritic cells (migDCs) are pivotal antigen-presenting that continuously transport antigens to draining lymph nodes and regulate immune responses. However, identification of migDCs is complicated by the lack distinguishing markers, it remains unclear which molecules determine their migratory capacity during inflammation. We show that, in skin, neuronal plasticity molecule activity-regulated cytoskeleton-associated protein/activity-regulated gene 3.1 (Arc/Arg3.1) was strictly...
Abstract Epidermal growth factor receptor (EGFR) ectodomain variants mediating primary resistance or secondary treatment failure in cancer patients treated with cetuximab panitumumab support the need for more resistance-preventive personalized ways of targeting this essential pathway. Here, we tested hypothesis that EGFR nanobody 7D12 fused to an IgG1 Fc portion (7D12-hcAb) would overcome ectodomain–mediated because it targets a very small binding epitope within domain III EGFR. Indeed,...
Esophagogastric adenocarcinoma (EGA) currently represents a main cause of cancer related death. Despite an intensified treatment for locally advanced or metastatic EGA with doublet chemotherapy consisting platinum compound and fluoropyrimidine in combination trastuzumab HER2-positive disease selected cases docetaxel, survival remains poor. Recently, immune-oncology based strategies relevantly improved the different solid tumors showed some promise late later stage trials EGA. Notably,...
Migratory dendritic cells (migDCs) continuously patrol tissues and are activated by injury inflammation. Extracellular adenosine triphosphate (ATP) is released damaged or actively secreted during inflammation increases migDC motility. However, the underlying molecular mechanisms which ATP accelerates migration not understood. Here, we show that migDCs can be distinguished from other DC subsets immune their expression of voltage-gated calcium channel subunit β3 (Cavβ3; CACNB3), exclusively...
<p>Supplementary Figure 1: The duration of response to various therapy lines for patients in the Ipi arm is depicted. For each line therapy, (DOR) indicated if applicable. Active represented by an arrow, and dashed arrows are used who were lost follow-up. Monotherapy with trastuzumab (T), ramucirumab (R), radiotherapy (#), or surgery (*) also indicated.</p>
<p>Supplementary Figure 3: Low NLR defines patients with superior survival in the Ipi arm.</p>
<p>Supplementary Figure 2: Emotional distress and tumor burden do not explain the systemic inflammatory signature.</p>
<div>Abstract<p>Anti–PD-1, trastuzumab, and chemotherapy are used in the treatment of patients with advanced HER2-positive esophagogastric adenocarcinoma, but long-term survival remains limited. In this study, we report extended follow-up data from INTEGA trial (NCT03409848), which investigated efficacy anti–PD-1 nivolumab, FOLFOX (FOLFOX arm) comparison a chemotherapy-free regimen involving anti–CTLA-4 ipilimumab (Ipi first-line setting for disease. The 12-month overall (OS)...
<p>Supplementary Figure 4: PFS in selected patients and overall survival of NLR > 5 patients. (A) months is shown for by CPS ≥ 1, HER2-3+, < within the Ipi arm (n=12). Median was 20.9 months. (B) Final vs FOLFOX >5 preselected Number at risk are indicated. Log-rank test performed (B).</p>
In metastatic colorectal cancer (mCRC), the efficacy of immune checkpoint blockade (ICB) has so far been limited to patients with microsatellite instability high tumors (MSI-H). Unfortunately, most mCRC suffer from non-immunogenic stable (MSS) tumors. Therefore, new combinatorial strategies are urgently needed enhance immunogenicity MSS finally increase number benefiting ICB.The AVETUX trial aimed combine PD-L1 antibody avelumab standard care chemotherapy combination FOLFOX and anti-EGFR...
Metastasis is a cancer-related systemic disease and responsible for the greatest mortality rate among cancer patients. Interestingly, interaction between immune system cells seems to play key role in metastasis formation target organ. However, this complex network only partially understood. We previously found that IL-22 produced by tissue resident iNKT17 promotes cell extravasation, early step of metastasis. Based on these data, we aimed here decipher last formation. levels were increased...
Objectives: To compare the feasibility and reliability of manual versus software-assisted assessments computed tomography scans according to iRECIST in patients undergoing immune-based cancer treatment. Methods: Computed 30 tumor treatment were evaluated by four independent radiologists at baseline (BL) two follow-ups (FU), resulting a total 360 (120 each BL/FU1/FU2). After image interpretation, burden response status either calculated manually or semi-automatically as defined software,...
Background Esophagogastric adenocarcinoma (EGA) presents a substantial global health challenge as the number of cases continues to rise. The current standard approach for treating localized EGA involves combination triplet chemotherapy, which consists platinum compound, fluoropyrimidine, and taxane (known FLOT), followed by surgery. In metastatic with HER2-positive status or in certain studies EGA, use HER2-targeted antibodies such trastuzumab has shown improved responses. Recently, addition...
Background The addition of nivolumab to trastuzumab and chemotherapy in first-line unresectable or metastatic HER2 positive esophagogastric adenocarcinoma (HER2+ EGA) results long progression-free overall survival as shown by the INTEGA (ipilimumab FOLFOX combination with adenocarcinoma) trial. This trial suggested that backbone is needed an unselected HER2+ patient population. Yet, it remains open question if there are specific subsets may benefit from enhanced immunotherapeutic but...