A5028608171- Immunotherapy and Immune Responses
- Cancer Immunotherapy and Biomarkers
- Immune Cell Function and Interaction
- CAR-T cell therapy research
- Immune cells in cancer
- Cancer Research and Treatments
- Monoclonal and Polyclonal Antibodies Research
- T-cell and B-cell Immunology
- Virus-based gene therapy research
- Cell Adhesion Molecules Research
- Glioma Diagnosis and Treatment
- Nanoplatforms for cancer theranostics
- Cancer Genomics and Diagnostics
- Cancer-related molecular mechanisms research
- Cytokine Signaling Pathways and Interactions
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Single-cell and spatial transcriptomics
- Pancreatic and Hepatic Oncology Research
- RNA modifications and cancer
- Mycobacterium research and diagnosis
- Glycosylation and Glycoproteins Research
- Phagocytosis and Immune Regulation
- RNA Interference and Gene Delivery
- Cardiac and Coronary Surgery Techniques
- Biosimilars and Bioanalytical Methods
Dana-Farber Cancer Institute
2014-2025
Novartis (United States)
2016-2024
Harvard University
2011-2023
Brigham and Women's Hospital
2010-2023
Dana-Farber Brigham Cancer Center
2009-2023
Novartis (Switzerland)
2016-2022
Novartis Institutes for BioMedical Research
2016-2022
Boston Biomedical Research Institute
2016-2021
Foundation for Biomedical Research
2018
Icahn School of Medicine at Mount Sinai
2017
Abstract Despite compelling antitumour activity of antibodies targeting the programmed death 1 (PD-1): ligand (PD-L1) immune checkpoint in lung cancer, resistance to these therapies has increasingly been observed. In this study, elucidate mechanisms adaptive resistance, we analyse tumour microenvironment context anti-PD-1 therapy two fully immunocompetent mouse models adenocarcinoma. tumours progressing following response therapy, observe upregulation alternative checkpoints, notably T-cell...
The success in lung cancer therapy with programmed death (PD)-1 blockade suggests that immune escape mechanisms contribute to tumor pathogenesis. We identified a correlation between EGF receptor (EGFR) pathway activation and signature of immunosuppression manifested by upregulation PD-1, PD-L1, CTL antigen-4 (CTLA-4), multiple tumor-promoting inflammatory cytokines. observed decreased CTLs increased markers T-cell exhaustion mouse models EGFR-driven cancer. PD-1 antibody improved the...
A large number of cancer-associated gene products evoke immune recognition, but host reactions rarely impede disease progression. The weak immunogenicity nascent tumors contributes to this failure in defense. Therapeutic vaccines that enhance dendritic cell presentation cancer antigens increase specific cellular and humoral responses, thereby effectuating tumor destruction some cases. attenuation T activation by cytotoxic lymphocyte-associated antigen 4 (CTLA-4) further limits the potency...
The in vivo function of murine granulocyte-macrophage colony-stimulating factor (GM-CSF) was investigated mice, carrying a null allele the GM-CSF gene, that were generated by gene targeting techniques embryonic stem cells. Although steady-state hematopoiesis unimpaired homozygous mutant animals, all animals developed progressive accumulation surfactant lipids and proteins alveolar space, defining characteristic idiopathic human disorder pulmonary proteinosis. Extensive lymphoid hyperplasia...
<h3>Objective</h3> Accumulating evidence links the intestinal microbiota and colorectal carcinogenesis. <i>Fusobacterium nucleatum</i> may promote tumour growth inhibit T cell-mediated immune responses against tumours. Thus, we hypothesised that amount of <i>F. in carcinoma might be associated with worse clinical outcome. <h3>Design</h3> We used molecular pathological epidemiology database 1069 rectal colon cancer cases Nurses' Health Study Professionals Follow-up Study, measured DNA tissue....
Pathways for presenting proteins from the extracellular fluids on MHC class I molecules have been described in macrophages. However, it is uncertain whether similar mechanisms exist dendritic cells, because conventional preparations of these cells can be contaminated with We addressed this issue by transducing granulocyte-macrophage CSF into bone marrow cultures followed supertransfection myc and raf oncogenes. These immortalized clones displayed morphology, many expressed cell-specific...
Cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) functions as a negative regulator of endogenous and vaccine-induced antitumor immunity. The administration fully human anti-CTLA-4 blocking monoclonal antibodies to advanced-cancer patients increases immune-mediated tumor destruction in some subjects. Nonetheless, that respond also frequently manifest serious inflammatory pathologies, raising the possibility therapeutic toxic effects CTLA-4 blockade might be linked. Here we show periodic...
We conducted a Phase I clinical trial investigating the biologic activity of vaccination with irradiated autologous melanoma cells engineered to secrete human granulocyte–macrophage colony-stimulating factor in patients metastatic melanoma. Immunization sites were intensely infiltrated T lymphocytes, dendritic cells, macrophages, and eosinophils all 21 evaluable patients. Although lesions resected before minimally immune system patients, after densely lymphocytes plasma showed extensive...
Abstract Immunosuppression is frequently associated with malignancy and particularly severe in patients malignant glioma. Anergy counterproductive shifts toward TH2 cytokine production are long-recognized T-cell defects these whose etiology has remained elusive for &gt;30 years. We show here that absolute counts of both CD4+ T cells CD4+CD25+FOXP3+CD45RO+ (Tregs) greatly diminished glioma, but Tregs represent an increased fraction the remaining CD4 compartment. This Treg fraction,...
Evidence indicates a complex link between gut microbiome, immunity, and intestinal tumorigenesis. To target the microbiota immunity for colorectal cancer prevention therapy, better understanding of relationship microorganisms immune cells in tumor microenvironment is needed. Experimental evidence suggests that Fusobacterium nucleatum may promote colonic neoplasia development by downregulating antitumor T cell-mediated adaptive immunity.To test hypothesis greater amount F carcinoma tissue...
Abstract STK11/LKB1 is among the most commonly inactivated tumor suppressors in non–small cell lung cancer (NSCLC), especially tumors harboring KRAS mutations. Many oncogenes promote immune escape, undermining effectiveness of immunotherapies, but it unclear whether inactivation suppressor genes, such as STK11/LKB1, exerts similar effects. In this study, we investigated consequences loss on microenvironment a mouse model KRAS-driven NSCLC. Genetic ablation resulted accumulation neutrophils...
Purpose: T-cell dysfunction is a hallmark of glioblastoma (GBM). Although anergy and tolerance have been well characterized, exhaustion remains relatively unexplored. Exhaustion, characterized in part by the upregulation multiple immune checkpoints, known contributor to failures amid checkpoint blockade, strategy that has lacked success thus far GBM. This study among first examine, credential as bona fide, T cells infiltrating human murine GBM.Experimental Design: Tumor-infiltrating...