A5062847058- Cancer Immunotherapy and Biomarkers
- Cancer Genomics and Diagnostics
- Pancreatic and Hepatic Oncology Research
- Lung Cancer Treatments and Mutations
- FOXO transcription factor regulation
- Cancer Research and Treatments
- Cancer Cells and Metastasis
- Epigenetics and DNA Methylation
- RNA modifications and cancer
- Immunotherapy and Immune Responses
- Ferroptosis and cancer prognosis
- Occupational and environmental lung diseases
- Lung Cancer Research Studies
- Lung Cancer Diagnosis and Treatment
- Circular RNAs in diseases
- Colorectal Cancer Treatments and Studies
- vaccines and immunoinformatics approaches
- Radiomics and Machine Learning in Medical Imaging
- Genetic factors in colorectal cancer
- Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis
- Cancer therapeutics and mechanisms
- Neuroendocrine Tumor Research Advances
- Monoclonal and Polyclonal Antibodies Research
- Immune cells in cancer
- Renal and related cancers
Bristol-Myers Squibb (United States)
2020-2025
Bayer (United States)
2025
Princeton University
2018-2022
Predictive Science (United States)
2022
University of Pennsylvania
2016-2021
Cancer Research Institute
2016-2021
UPMC Hillman Cancer Center
2018-2021
Cancer Research Center
2021
Cincinnati Children's Hospital Medical Center
2009-2020
Advaxis (United States)
2018-2020
Neoadjuvant or adjuvant chemotherapy confers a modest benefit over surgery alone for resectable non–small-cell lung cancer (NSCLC). In early-phase trials, nivolumab-based neoadjuvant regimens have shown promising clinical activity; however, data from phase 3 trials are needed to confirm these findings.
The expanding number of targeted therapeutics for non-small cell lung cancer (NSCLC) necessitates real-time tumor genotyping, yet tissue biopsies are difficult to perform serially and often yield inadequate DNA next-generation sequencing (NGS). We evaluated the feasibility using cell-free circulating (ctDNA) NGS as a complement or alternative NGS.A total 112 plasma samples obtained from consecutive study 102 prospectively enrolled patients with advanced NSCLC were subjected ultra-deep up 70...
Abstract Purpose: Immunotherapy has the potential to improve dismal prognosis in pancreatic ductal adenocarcinoma (PDA), but clinical trials, including those with single-agent PD-1 or PD-L1 inhibition, have been disappointing. Our aim was examine immune landscape of PDA as it relates aspects tumor biology, neoepitope burden. Experimental Design: We used publicly available expression data from 134 primary resection samples The Cancer Genome Atlas stratify patients according a cytolytic T-cell...
•With a ≥3-year follow-up in CheckMate 743, nivolumab + ipilimumab continued to provide long-term OS benefit first-line MPM.•Clinical benefits remained consistent across patient subgroups, including epithelioid versus non-epithelioid histology.•Discontinuing due TRAEs did not negatively impact benefit.•Nivolumab continues be an efficacious treatment option for patients with unresectable MPM. BackgroundIn the phase III 743 study (NCT02899299), plus significantly improved overall survival (OS)...
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...
<h2>Abstract</h2><h3>Introduction</h3> In the phase 3 CheckMate 9LA study, nivolumab plus ipilimumab with chemotherapy prolonged overall survival (OS) versus alone. We report updated efficacy/safety (≥3 years' follow-up), clinical outcomes in patients baseline brain metastases, and exploratory somatic mutation analyses. <h3>Methods</h3> Adults stage IV/recurrent non–small cell lung cancer (NSCLC), no known sensitizing <i>EGFR</i>/<i>ALK</i> alterations, Eastern Cooperative Oncology Group...
Abstract The immune system exerts antitumor activity via T cell–dependent recognition of tumor-specific antigens. Although the number tumor neopeptides—peptides derived from somatic mutations—often correlates with and survival, most classically defined high-affinity neopeptides (CDNs) are not immunogenic, only rare CDNs have been linked to rejection. Thus, rules antigen remain incompletely understood. Here, we analyzed neopeptides, activity, clinical outcome 6,324 patients across 27 types....
Abstract The degree of metastatic disease varies widely among patients with cancer and affects clinical outcomes. However, the biological functional differences that drive extent metastasis are poorly understood. We analyzed primary tumors paired metastases using a multifluorescent lineage-labeled mouse model pancreatic ductal adenocarcinoma (PDAC)—a tumor type in which most present metastases. Genomic transcriptomic analysis revealed an association between burden gene amplification or...
•Primary endpoint of OS with nivolumab plus chemotherapy versus in nonsquamous metastatic NSCLC was not met.•Descriptive analyses showed improved all-randomized and squamous populations.•PFS DOR favored populations.•No firm associations were found between select somatic mutations, TMB, or LIPI score chemotherapy.•Safety consistent previous reports, no new safety signals identified. BackgroundIn CheckMate 227 Part 1, first-line ipilimumab prolonged overall survival (OS) patients...
Comprehensive molecular analysis of rare circulating tumor cells (CTCs) and cell clusters is often hampered by low throughput purity, as well loss. To address this, we developed a fully integrated platform for flow cytometry-based isolation CTCs from blood that can be combined with whole transcriptome or targeted RNA transcript quantification. Downstream signature linked to phenotype through index sorting. This newly utilizes in-line magnetic particle-based leukocyte depletion, acoustic...
Abstract Despite known histological, biological, and clinical differences between lung adenocarcinoma (LUAD) squamous cell carcinoma (LUSC), relatively little is about the spatial in their corresponding immune contextures. Our study of over 1000 LUAD LUSC tumors revealed that computationally derived patterns tumor-infiltrating lymphocytes (TILs) on H&E images were different ( N = 421) 438), with TIL density being prognostic overall survival arrangement more prognostically relevant LUSC....
Abstract The tumor immune composition influences prognosis and treatment sensitivity in lung cancer. presence of effective adaptive responses is associated with increased clinical benefit after checkpoint blockers. Conversely, immunotherapy resistance can occur as a consequence local T-cell exhaustion/dysfunction upregulation immunosuppressive signals regulatory cells. Consequently, merely measuring the amount tumor-infiltrating lymphocytes (TILs) may not accurately reflect complexity...
Abstract Vascular endothelial cells provide essential support to the tumor microenvironment, but little is known about transcriptional control of functions during tumorigenesis. Here we define a critical role for Forkhead transcription factor FoxM1 in modulating development tumor-associated cells. Pulmonary tumorigenesis induced by urethane administration was compared mice genetically deleted (enFoxm1−/− mice). Notably, lung number and size were increased enFoxm1−/− mice. Increased...
The treatment of advanced prostate cancer (PCa) remains a challenge. Identification new molecular mechanisms that regulate PCa initiation and progression would provide targets for the development treatments. Foxm1 transcription factor is highly up-regulated in tumor cells, inflammatory cells microenvironment. However, its functions different cell populations lesions are unknown. To determine role during development, we generated two novel transgenic mouse models, one exhibiting...
Lung cancer remains one of the most prominent public health challenges, accounting for highest incidence and mortality among all human cancers. While pulmonary invasive mucinous adenocarcinoma (PIMA) is aggressive types non-small cell lung cancer, transcriptional drivers PIMA remain poorly understood. In present study, we found that Forkhead box M1 transcription factor (FOXM1) highly expressed in PIMAs associated with increased extracellular mucin deposition loss NKX2.1. To examine...
Idiopathic pulmonary fibrosis (IPF) is a chronic disease with high mortality and refractory to treatment. Pulmonary macrophages can both promote repress fibrosis, however molecular mechanisms regulating macrophage functions during remain poorly understood. FOXM1 transcription factor not expressed in quiescent lungs. Herein, we show that highly within fibrotic lungs of IPF patients mouse Macrophage-specific deletion Foxm1 mice (myFoxm1-/-) exacerbated fibrosis. Inactivation vivo vitro...
PURPOSE Neoadjuvant immune checkpoint blockade with nivolumab plus ipilimumab improves overall survival (OS) in non–small cell lung cancer (NSCLC); however, randomized data for resectable are limited. We report results from the exploratory concurrently and chemotherapy arms of international phase III CheckMate 816 trial. METHODS Adults stage IB-IIIA (American Joint Committee on Cancer seventh edition) NSCLC received three cycles once every 2 weeks one cycle or (on day 1 days 8 each 3-week...
635 Background: The optimal treatment for patients (pts) with advanced HCC who progress on an ICI-containing regimen has not been defined. In pts progressed one prior ICI regimen, regorafenib plus pembrolizumab (rego + pembro) showed modest anti-tumor activity (primary completion analysis: overall objective response rate 7.4%, all partial responses [PR]) and expected safety profile (NCT04696055; El-Khoueiry, ASCO 2024). We conducted additional exploratory analyses of tumor markers to gain...