A5058975989- Cancer Immunotherapy and Biomarkers
- Lung Cancer Treatments and Mutations
- Lymphoma Diagnosis and Treatment
- Cancer Genomics and Diagnostics
- RNA modifications and cancer
- Immunotherapy and Immune Responses
- Immune Cell Function and Interaction
- Chronic Lymphocytic Leukemia Research
- CAR-T cell therapy research
- Lung Cancer Research Studies
- Colorectal Cancer Treatments and Studies
- Genetic factors in colorectal cancer
- Cancer-related gene regulation
- Peptidase Inhibition and Analysis
- Monoclonal and Polyclonal Antibodies Research
- Sarcoma Diagnosis and Treatment
- Head and Neck Cancer Studies
- Viral-associated cancers and disorders
- Immune cells in cancer
- Melanoma and MAPK Pathways
- Multiple Myeloma Research and Treatments
- Single-cell and spatial transcriptomics
- Galectins and Cancer Biology
- Cell Adhesion Molecules Research
- Cervical Cancer and HPV Research
Brigham and Women's Hospital
2016-2025
Harvard University
2016-2025
Dana-Farber Cancer Institute
2016-2025
Dana-Farber Brigham Cancer Center
2013-2025
Massachusetts General Hospital
2009-2023
Women's Hospital
2011-2023
The University of Texas MD Anderson Cancer Center
2002-2021
Weatherford College
2021
Roche (Switzerland)
2019
Gilead Sciences (United States)
2019
Preclinical studies suggest that Reed-Sternberg cells exploit the programmed death 1 (PD-1) pathway to evade immune detection. In classic Hodgkin's lymphoma, alterations in chromosome 9p24.1 increase abundance of PD-1 ligands, PD-L1 and PD-L2, promote their induction through Janus kinase (JAK)-signal transducer activator transcription (STAT) signaling. We hypothesized nivolumab, a PD-1-blocking antibody, could inhibit tumor evasion patients with relapsed or refractory lymphoma.In this...
Understanding the interactions between tumor and host immune system is critical to finding prognostic biomarkers, reducing drug resistance, developing new therapies. Novel computational methods are needed estimate tumor-infiltrating cells understand tumor–immune in cancers. We analyze over 10,000 RNA-seq samples across 23 cancer types from The Cancer Genome Atlas (TCGA). Our computationally inferred infiltrates associate much more strongly with patient clinical features, viral infection...
The EML4-ALK fusion oncogene represents a novel molecular target in small subset of non-small-cell lung cancers (NSCLC). To aid identification and treatment these patients, we examined the clinical characteristics outcomes patients who had NSCLC with without EML4-ALK.Patients were selected for genetic screening on basis two or more following characteristics: female sex, Asian ethnicity, never/light smoking history, adenocarcinoma histology. was identified by using fluorescent situ...
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...
Waldenström's macroglobulinemia is an incurable, IgM-secreting lymphoplasmacytic lymphoma (LPL). The underlying mutation in this disorder has not been delineated.We performed whole-genome sequencing of bone marrow LPL cells 30 patients with macroglobulinemia, paired normal-tissue and tumor-tissue 10 patients. Sanger was used to validate the findings samples from expanded cohort LPL, those other B-cell disorders that have some same features as healthy donors.Among a somatic variant (T→C)...
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...
Cancer cells can exploit the programmed death-1 (PD-1) immune checkpoint pathway to avoid surveillance by modulating T-lymphocyte activity. In part, this may occur through overexpression of PD-1 and ligands (PD-L1 PD-L2) in tumor microenvironment. blockade has produced significant antitumor activity solid tumors, similar evidence emerged hematologic malignancies.In phase I, open-label, dose-escalation, cohort-expansion study, patients with relapsed or refractory B-cell lymphoma, T-cell...
MYD88(L265P) and CXCR4(WHIM) mutations are highly prevalent in Waldenström's macroglobulinemia. triggers tumor-cell growth through Bruton's tyrosine kinase, a target of ibrutinib. confer vitro resistance to ibrutinib.We performed prospective study ibrutinib 63 symptomatic patients with macroglobulinemia who had received at least one previous treatment, we investigated the effect MYD88 CXCR4 on outcomes. Ibrutinib daily dose 420 mg was administered orally until disease progression or...
Inflammatory myofibroblastic tumor (IMT) is a distinctive mesenchymal neoplasm characterized by spindle-cell proliferation with an inflammatory infiltrate. Approximately half of IMTs carry rearrangements the anaplastic lymphoma kinase (ALK) locus on chromosome 2p23, causing aberrant ALK expression. We report sustained partial response to inhibitor crizotinib (PF-02341066, Pfizer) in patient ALK-translocated IMT, as compared no observed activity another without translocation. These results...
Abstract Purpose: Programmed cell death ligand 1 (PD-L1) is an immunomodulatory molecule expressed by antigen-presenting cells and select tumors that engages receptors on T to inhibit T-cell immunity. Immunotherapies targeting the PD-1/PD-L1 pathway have shown durable antitumor effects in a subset of patients with solid tumors. PD-L1 can be Reed–Sternberg comprising classical Hodgkin lymphoma (CHL) malignant B EBV-positive posttransplant lymphoproliferative disorders (PTLD). We sought...
Classical Hodgkin lymphomas (cHLs) include small numbers of malignant Reed-Sternberg cells within an extensive but ineffective inflammatory/immune cell infiltrate. In cHL, chromosome 9p24.1/PD-L1/PD-L2 alterations increase the abundance PD-1 ligands, PD-L1 and PD-L2, their further induction through Janus kinase 2-signal transducers activators transcription signaling. The unique composition cHL limits its analysis with high-throughput genomic assays. Therefore, precise incidence, nature,...
Diffuse large B cell lymphoma (DLBCL) is a biologically heterogeneous and clinically aggressive disease. Here, we explore the role of bromodomain extra-terminal domain (BET) proteins in DLBCL, using integrative chemical genetics functional epigenomics. We observe highly asymmetric loading 4 (BRD4) at enhancers, with approximately 33% all BRD4 localizing to enhancers 1.6% occupied genes. These super-enhancers prove particularly sensitive inhibition, explaining selective effect BET inhibitors...
The anaplastic large cell kinase gene (ALK) is rearranged in approximately 5% of lung adenocarcinomas within the Asian population. We evaluated incidence and characteristics ALK-rearranged western population optimal diagnostic modality to detect ALK rearrangements routine clinical practice.We tested 358 from three institutions for by fluorescent situ hybridization (FISH) immunohistochemistry with without tyramide amplification. clinicopathologic tumors were compared.We identified 20 (5.6%)...
Abstract Purpose: Programmed cell death ligand 1 (PD-L1) is a molecule expressed on antigen-presenting cells that engages the PD-1 receptor T and inhibits T-cell signaling. The axis can be exploited by tumor to dampen host antitumor immune responses foster survival. blockade has shown promise in multiple malignancies but should directed toward patients whom it will most effective. In recent studies, we found chromosome 9p24.1 amplification increased gene dosage of PD-L1 its induction JAK2...