A5068945817- Pancreatic and Hepatic Oncology Research
- Cancer Genomics and Diagnostics
- Epigenetics and DNA Methylation
- Cancer Immunotherapy and Biomarkers
- Cancer Cells and Metastasis
- Immunotherapy and Immune Responses
- Neuroendocrine Tumor Research Advances
- Pancreatitis Pathology and Treatment
- Radiomics and Machine Learning in Medical Imaging
- Single-cell and spatial transcriptomics
- Sarcoma Diagnosis and Treatment
- Bone and Dental Protein Studies
- Renal cell carcinoma treatment
- Ferroptosis and cancer prognosis
- Cancer Research and Treatments
- CAR-T cell therapy research
- Immune cells in cancer
- Cholangiocarcinoma and Gallbladder Cancer Studies
- Genetic factors in colorectal cancer
- Monoclonal and Polyclonal Antibodies Research
- Gastric Cancer Management and Outcomes
- Immune Cell Function and Interaction
- TGF-β signaling in diseases
- Colorectal and Anal Carcinomas
- Lymphoma Diagnosis and Treatment
Johns Hopkins Medicine
2016-2025
Johns Hopkins University
2016-2025
Cancer Research Center
2018-2025
Sidney Kimmel Comprehensive Cancer Center
2018-2024
Bloomberg (United States)
2018-2024
University of Baltimore
2024
Yale University
2023
Yale Cancer Center
2023
Sidney Kimmel Cancer Center
2019-2021
Oregon Health & Science University
2020
Neoadjuvant anti-PD-1 may improve outcomes for patients with resectable NSCLC and provides a critical window examining pathologic features associated response. Resections showing major response to neoadjuvant therapy, defined as ≤10% residual viable tumor (RVT), predict improved long-term patient outcome. However, %RVT calculations were developed in the context of chemotherapy (%cRVT). An immune-related (%irRVT) has yet be developed.The first trial (nivolumab, NCT02259621) was just reported....
<h3>Objective</h3> Recent data supports a significant role for immune checkpoint inhibitors in the treatment of solid tumours. Here, we evaluate gastric and gastro-oesophageal junction (G/GEJ) adenocarcinomas their expression programmed death-ligand 1 (PD-L1), infiltration by CD8+ T cells relationship both factors to patient survival. <h3>Design</h3> Thirty-four resections primary invasive G/GEJ were stained immunohistochemistry PD-L1 CD8 DNA situ hybridisation Epstein–Barr virus (EBV). cell...
Pancreatic cysts are common and often pose a management dilemma, because some precancerous, whereas others have little risk of developing into invasive cancers. We used supervised machine learning techniques to develop comprehensive test, CompCyst, guide the patients with pancreatic cysts. The test is based on selected clinical features, imaging characteristics, cyst fluid genetic biochemical markers. Using data from 436 cysts, we trained CompCyst classify as those who required surgery,...
Background & AimsNext-generation sequencing (NGS) of pancreatic cyst fluid is a useful adjunct in the assessment patients with cyst. However, previous studies have been retrospective or single institutional experiences. The aim this study was to prospectively evaluate NGS on multi-institutional cohort real time.MethodsThe performance 22-gene panel (PancreaSeq) first retrospectively confirmed and then within 2-year timeframe, PancreaSeq testing used endoscopic ultrasound–guided fine-needle...
Successful pancreatic ductal adenocarcinoma (PDAC) immunotherapy necessitates optimization and maintenance of activated effector T cells (Teff). We prospectively collected applied multi-omic analyses to paired pre- post-treatment PDAC specimens in a platform neoadjuvant study granulocyte-macrophage colony-stimulating factor-secreting allogeneic vaccine (GVAX) ± nivolumab (anti-programmed cell death protein 1 [PD-1]) uncover sensitivity resistance mechanisms. show that GVAX-induced tertiary...
Abstract Neoadjuvant immunotherapy plus chemotherapy improves event-free survival (EFS) and pathologic complete response (0% residual viable tumor (RVT) in primary (PT) lymph nodes (LNs)), is approved for treatment of resectable lung cancer. Pathologic assessment after neoadjuvant therapy the potential analog to radiographic advanced disease. However, %RVT thresholds beyond major (≤10% RVT) have not been explored. was prospectively assessed randomized, phase 3 CheckMate 816 trial...
Abstract Gastroesophageal cancer dynamics and drivers of clinical responses with immune checkpoint inhibitors (ICI) remain poorly understood. Potential synergistic activity dual programmed cell death protein 1 (PD-1) lymphocyte-activation gene 3 (LAG-3) inhibition may help improve immunotherapy for these tumors. We report a phase Ib trial that evaluated neoadjuvant nivolumab (Arm A, n = 16) or nivolumab–relatlimab B, in combination chemoradiotherapy 32 patients resectable stage II/stage III...
Studies of T cell responses to tumors have focused on the draining lymph node (LN) as site activation. We examined tumor mass a potential activation after adoptive transfer naive tumor-specific CD8 cells. Activated cells were present in within 24 h and proliferation these was also evident 4-5 d later mice treated with FTY720 prevent infiltration activated LNs. To confirm that occurred not tumor-draining LNs, we used lacking proliferating tumor-infiltrating lymphocytes 4 transfer. acquired...
The presence of lymph node (LN)-like vasculature in tumours, characterized by expression peripheral addressin and chemokine CCL21, is correlated with T-cell infiltration positive prognosis breast cancer melanoma patients. However, mechanisms controlling the development LN-like how it might contribute to a beneficial outcome for patients are unknown. Here we demonstrate that present murine models lung carcinoma. It enables naive T cells significantly delay tumour outgrowth after intratumoral...
Abstract Purpose: Pathologic response assessment of tumor specimens from patients receiving systemic treatment provides an early indication therapeutic efficacy and predicts long-term survival. Grading systems for pathologic were first developed chemotherapy in select types. Immunotherapeutic agents have a mechanism action distinct are being used across broad array A standardized, universal scoring system that encompasses features characteristic immunotherapy spans types is needed....
Abstract Intraductal papillary mucinous neoplasms (IPMNs) and cystic (MCNs) are non-invasive that often observed in association with invasive pancreatic cancers, but their origins evolutionary relationships poorly understood. In this study, we analyze 148 samples from IPMNs, MCNs, small associated carcinomas 18 patients using whole exome or targeted sequencing. Using analyses, establish both IPMNs MCNs direct precursors to cancer. Mutations SMAD4 TGFBR2 frequently restricted carcinoma, while...
Immunotherapy has demonstrated a limited clinical efficacy in approximately 5% of cholangiocarcinoma. The main challenges for an effective immunotherapy response cholangiocarcinoma arise from the tumor microenvironment, which is poorly understood.
Abstract A neoadjuvant immunotherapy platform clinical trial allows for rapid evaluation of treatment-related changes in tumors and identifying targets to optimize treatment responses. We enrolled patients with resectable pancreatic adenocarcinoma into such a (NCT02451982) receive cancer GVAX vaccine low-dose cyclophosphamide alone (Arm A; n = 16), anti-PD-1 antibody nivolumab B; 14), both anti-CD137 agonist urelumab C; 10), respectively. The primary endpoint Arms A/B - change IL17A...
Radiotherapy is hypothesized to have an immune-modulating effect on the tumor microenvironment (TME) of pancreatic ductal adenocarcinoma (PDAC) sensitize it anti-PD-1 antibody (a-PD-1) treatment. We collected paired pre- and posttreatment specimens from a clinical trial evaluating combination treatment with GVAX vaccine, a-PD-1, stereotactic body radiation (SBRT) following chemotherapy for locally advanced PDACs (LAPC). With resected different neoadjuvant therapies as comparisons, effector...
Large cell neuroendocrine carcinoma (LCNEC) is a high-grade neoplasm first described in the lung and subsequently well documented many other anatomic sites. It has only recently been recognized that LCNEC can also occasionally arise head neck. The role of human papillomavirus (HPV), which associated with some small carcinomas neck, not investigated for LCNEC. We sought to further characterize histologic, immunophenotypic, clinical features investigate HPV this newly group tumors. surgical...
Abstract Pancreatic ductal adenocarcinoma (PDAC) is an aggressive malignancy characterized by extensive local invasion and systemic spread. In this study, we employed a three-dimensional organoid model of human pancreatic cancer to characterize the molecular alterations critical for invasion. Time-lapse microscopy was used observe in organoids from 25 surgically resected PDAC samples collagen I. Subsequent lentiviral modification small-molecule inhibitors were investigate programs underlying...
Abstract Background Mismatch repair proficient (MMRp) colorectal cancer (CRC) has been refractory to single‐agent programmed cell death protein 1 (PD1) inhibitor therapy. Colon GVAX is an allogeneic, whole‐cell, granulocyte‐macrophage colony‐stimulating factor ‐secreting cellular immunotherapy that induces T‐cell immunity against tumor‐associated antigens and previously studied in combination with low‐dose cyclophosphamide (Cy) inhibit regulatory T cells. Methods We conducted a single‐arm...
Intraductal papillary mucinous neoplasms (IPMNs) are non-invasive precursor lesions that can progress to invasive pancreatic cancer and classified as low-grade or high-grade based on the morphology of neoplastic epithelium. We aimed compare genetic alterations in regions same IPMN order identify molecular underlying progression.We performed multiregion whole exome sequencing tissue samples from 17 IPMNs with both dysplasia (76 regions, including 49 27 dysplasia). reconstructed phylogeny for...
Clinical trials with immune checkpoint inhibition in sarcomas have demonstrated minimal response. Here, we interrogated the tumor microenvironment (TME) of two contrasting soft-tissue (STS), rhabdomyosarcomas and undifferentiated pleomorphic (UPS), differing genetic underpinnings responses to understand mechanisms that lead response.Utilizing fresh formalin-fixed, paraffin-embedded tissue from patients diagnosed UPS rhabdomyosarcomas, dissected TME by using IHC, flow cytometry, comparative...