A5070820869- CAR-T cell therapy research
- Lung Cancer Treatments and Mutations
- Immunotherapy and Immune Responses
- Virus-based gene therapy research
- Cancer Immunotherapy and Biomarkers
- Redox biology and oxidative stress
- RNA modifications and cancer
- Cancer-related molecular mechanisms research
- Cancer Research and Treatments
- Cancer Cells and Metastasis
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Genomics, phytochemicals, and oxidative stress
- Lung Cancer Diagnosis and Treatment
- RNA Interference and Gene Delivery
- Immune cells in cancer
- Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis
- Heat shock proteins research
- Glutathione Transferases and Polymorphisms
- Inflammasome and immune disorders
- Ferroptosis and cancer prognosis
- Lung Cancer Research Studies
University of Basel
2023-2025
University Hospital of Basel
2020-2024
ShanghaiTech University
2020
ETH Zurich
2019-2020
University of Zurich
2017
Abstract In solid tumors, the presence of lymph node–like structures called tertiary lymphoid (TLS) is associated with improved patient survival. However, little known about how TLS develop in cancer, their function affects survival, and whether they are affected by cancer therapy. this study, we used multispectral microscopy, quantitative pathology, gene expression profiling to analyze formation human lung squamous cell carcinoma (LSCC) an experimental model induction. We identified a niche...
Aerobic organisms need to maintain cellular redox homeostasis. Glutathione peroxidase-4 (Gpx4) has the unique ability protect cells against lipid peroxidation. Here, we show that Gpx4 is absolutely required prevent ferroptosis during development, maintenance, and responses of innate-like B cells, namely, B1 marginal zone (MZ) cells. In contrast, dispensable for germinal center reactions, antibody follicular B2 Mechanistically, increased metabolism sensitivity peroxidation in MZ compared...
Antioxidant systems, such as the thioredoxin-1 (Trx1) pathway, ensure cellular redox homeostasis. However, how systems regulate development and function of myeloid cells is barely understood. Here we show that in contrast to its critical role T cells, murine Trx1 system dispensable for steady-state myeloid-cell hematopoiesis due their capacity tap glutathione/glutaredoxin pathway DNA biosynthesis. instrumentally enables nuclear NF-κB DNA-binding thereby pro-inflammatory responses monocytes...
Thioredoxin-1 (Trx1) is a vital component for cellular redox homeostasis. In T cells, Trx1 donates electrons the de novo synthesis of deoxyribonucleotides to allow rapid cell proliferation. The Trx-interacting protein (Txnip) binds reduced and inhibits its activity. However, role Txnip in adaptive immunity vivo unknown. Here, we show that absence increased proliferation effector cells GC B-cell responses response lymphocytic choriomeningitis virus Qβ virus-like particles, respectively, but...
Adoptive cell therapy (ACT) with tumor-infiltrating lymphocytes (TIL) is effective in patients melanoma, although long-term responses seem restricted who have complete remissions. Many develop secondary resistance to TIL-ACT but the involved mechanisms are unclear. In this study, we describe a case of possibly due intratumoral heterogeneity and selection resistant tumor clone by transferred T cells. To best our knowledge, first clonal pre-existing nondominant clone; report demonstrates...
Antioxidant systems maintain cellular redox homeostasis. The thioredoxin-1 (Trx1) and the glutathione (GSH)/glutaredoxin-1 (Grx1) are key players in preserving cytosolic balance. In fact, T lymphocytes critically rely on reducing equivalents from Trx1 system for DNA biosynthesis during metabolic reprogramming upon activation. We here show that is also indispensable development functionality of marginal zone (MZ) B cells B1 mice. contrast, conventional cells, follicular B-cell homeostasis,...
Abstract CAR T-cell therapy has improved outcomes for patients with chemotherapy-resistant B-cell malignancies. However, treatment of solid cancers been more difficult, in part because the heterogeneous expression tumor-specific cell surface antigens. Here, we describe generation a fully human targeting altered glycosylation secretory epithelial cancers. The target antigen – truncated, sialylated O-glycan sialyl-Thomsen-Nouveau (STn) was studied highly STn-specific antibody across various...
Adoptive cell therapy (ACT) with tumor-infiltrating lymphocytes (TIL) is a personalized immunotherapy. The efficacy of TIL-ACT has been demonstrated prospectively in patients advanced melanoma but not limited to patients. Many are refractory TIL-ACT, however, or their cancer becomes resistant. Combining anti-programmed death protein 1 (anti-PD-1) antagonize the immunosuppressive tumor microenvironment may synergize enhance antitumor potential. We set up Between 2020 and 2022, we enrolled 11...
<div>Abstract<p>Adoptive cell therapy (ACT) with tumor-infiltrating lymphocytes (TIL) is effective in patients melanoma, although long-term responses seem restricted who have complete remissions. Many develop secondary resistance to TIL-ACT but the involved mechanisms are unclear. In this study, we describe a case of possibly due intratumoral heterogeneity and selection resistant tumor clone by transferred T cells. To best our knowledge, first clonal pre-existing nondominant...
<div>Abstract<p>Adoptive cell therapy (ACT) with tumor-infiltrating lymphocytes (TIL) is effective in patients melanoma, although long-term responses seem restricted who have complete remissions. Many develop secondary resistance to TIL-ACT but the involved mechanisms are unclear. In this study, we describe a case of possibly due intratumoral heterogeneity and selection resistant tumor clone by transferred T cells. To best our knowledge, first clonal pre-existing nondominant...
<p>Supplementary Figure 2. Regressing soft tissue metastasis (Biopsy 3 weeks after TIL transfer). Vital tumor areas (SOX10) are densely infiltrated by CD8 positive infiltrating lymphocytes as shown immunohistochemistry.</p>
<p>Supplementary Figure 5. Reactivity assay of TIL product to the primary tumor. CD3+ T cells from were tested for intracellular cytokine upregulation against a tumor cell line (TCL) derived resected lesion. Anti-CD3/CD28 stimulation was used as positive control. As negative control, we HLA blockade.</p>
<p>Supplementary Data</p>
<p>Supplementary Figure 1. Study Design of the <i>BaseTIL</i> trial. The trial was a phase I tumor-infiltrating lymphocyte (TIL) therapy in combination with low dose interleukin-2 (IL2) and PD1 blockade nivolumab for patients metastatic melanoma.</p>
<p>Supplementary Figure 4. Progressing lung metastasis (Wedge resection 61 weeks after TIL transfer). The resected is Melan-A positive without any desmoplastic component.</p>
<p>Supplementary Figure 1. Study Design of the <i>BaseTIL</i> trial. The trial was a phase I tumor-infiltrating lymphocyte (TIL) therapy in combination with low dose interleukin-2 (IL2) and PD1 blockade nivolumab for patients metastatic melanoma.</p>
<p>Supplementary Data</p>
<p>Supplementary Figure 6. Expression analysis of selected exhaustion markers on different T cells in the tumor lesion used for TIL expansion.</p>
<p>Supplementary Figure 2. Regressing soft tissue metastasis (Biopsy 3 weeks after TIL transfer). Vital tumor areas (SOX10) are densely infiltrated by CD8 positive infiltrating lymphocytes as shown immunohistochemistry.</p>
<p>Supplementary Figure 3. Regressing soft tissue metastasis (Biopsy 10 weeks after TIL transfer). No vital tumor is detectable.</p>
<p>Supplementary Figure 6. Expression analysis of selected exhaustion markers on different T cells in the tumor lesion used for TIL expansion.</p>
<p>Supplementary Figure 3. Regressing soft tissue metastasis (Biopsy 10 weeks after TIL transfer). No vital tumor is detectable.</p>
<p>Supplementary Figure 7. MHC I expression on tumor cells in lesion used for expansion of the TIL product and progressing lung metastasis.</p>
<p>Supplementary Figure 7. MHC I expression on tumor cells in lesion used for expansion of the TIL product and progressing lung metastasis.</p>
<p>Supplementary Figure 4. Progressing lung metastasis (Wedge resection 61 weeks after TIL transfer). The resected is Melan-A positive without any desmoplastic component.</p>