A5035640196- Cancer Immunotherapy and Biomarkers
- Renal cell carcinoma treatment
- CAR-T cell therapy research
- Pancreatic and Hepatic Oncology Research
- Cancer Genomics and Diagnostics
- Epigenetics and DNA Methylation
- Bladder and Urothelial Cancer Treatments
- Immunotherapy and Immune Responses
- Ferroptosis and cancer prognosis
- Single-cell and spatial transcriptomics
- RNA modifications and cancer
- Ocular Diseases and Behçet’s Syndrome
- Metastasis and carcinoma case studies
- Infectious Diseases and Tuberculosis
- Immune cells in cancer
- Political and Social Issues
- Peptidase Inhibition and Analysis
- Cholangiocarcinoma and Gallbladder Cancer Studies
- Rheumatoid Arthritis Research and Therapies
- Cancer Diagnosis and Treatment
- Otitis Media and Relapsing Polychondritis
- Medical Imaging and Pathology Studies
- Political Philosophy and Ethics
- Cancer, Hypoxia, and Metabolism
- Vasculitis and related conditions
Brigham and Women's Hospital
2022-2025
Yale University
2025
Harvard University
2023-2024
Dana-Farber Cancer Institute
2023
Lemuel Shattuck Hospital
2023
American University of Beirut
2020
American University of Beirut Medical Center
2020
While the mutational and transcriptional landscapes of renal cell carcinoma (RCC) are well-known, epigenome is poorly understood. We characterize clear (ccRCC), papillary (pRCC), chromophobe RCC (chRCC) by using ChIP-seq, ATAC-Seq, RNA-seq, SNP arrays. integrate 153 individual data sets from 42 patients nominate 50 histology-specific master transcription factors (MTF) to define histologic subtypes, including EPAS1 ETS-1 in ccRCC, HNF1B pRCC, FOXI1 chRCC. confirm MTFs via immunohistochemistry...
Abstract Immune checkpoint inhibitors (ICI) targeting the PD-1 pathway have transformed treatment of advanced renal cell carcinoma (RCC), but mechanisms underlying therapeutic response remain largely unknown. Herein, we perform transcriptomic analysis on RCC biospecimens from 102 patients enrolled in a phase II clinical trial frontline nivolumab (NCT03117309) to investigate determinants anti-PD1 monotherapy. Through bulk analysis, identify an enrichment genes associated with tertiary...
Abstract Purpose: Programmed cell death protein 1 (PD-1) expression on CD8+TIM-3−LAG-3− tumor-infiltrating cells predicts positive response to PD-1 blockade in metastatic clear-cell renal carcinoma (mccRCC). Because inhibition of signaling regulatory T (Treg) augments their immunosuppressive function, we hypothesized that Tregs would predict resistance inhibitors. Experimental Design: PD-1+ were phenotyped using multiparametric immunofluorescence ccRCC tissues from the CheckMate-025 trial...
590 Background: Inhibition of PD-1 signaling in regulatory T cells (Tregs) has been shown to enhance their immunosuppressive function. We previously demonstrated that high levels expression on tumor-infiltrating Tregs are associated with resistance nivolumab (nivo) monotherapy pretreated patients advanced clear cell renal carcinoma (ccRCC) from the CheckMate-025 trial (Denize et al, 2024). Here, we aim validate these findings first-line setting. Methods: Primary tumor tissues ccRCC (n=70)...
591 Background: TLS are organized lymphoid aggregates linked to improved response immunotherapy in multiple cancers, including mRCC. Traditionally, assessment relies on pathological staining of tumor sections. In this study, we evaluated the performance gene-expression signatures as an alternative diagnostic tool. Methods: Primary tumors from treatment-naïve patients with mRCC HCRN GU16-260 trial were analyzed using multiparametric immunofluorescence (IF), for CD3, CD20 (TLS), CD21 (mature...
Renal cell carcinoma with sarcomatoid differentiation (sRCC) is associated poor survival and a heightened response to immune checkpoint inhibitors (ICIs). Two major barriers improving outcomes for sRCC are the limited understanding of its gene regulatory programs low diagnostic yield tumor biopsies due spatial heterogeneity. Herein, we characterized epigenomic landscape by profiling 107 libraries from tissue plasma samples 50 patients RCC healthy volunteers. By histone modifications DNA...
Autologous therapeutic tumor-infiltrating lymphocyte (TIL) therapy is a promising strategy to enhance antitumor immunity. Optimization of ex vivo TIL expansion could expand current immunotherapy options. Previous attempts generate in renal cell carcinoma (RCC) have been technically challenging. We applied second-generation manufacturing process, currently used the melanoma product lifileucel, RCC. Resected primary and metastatic RCC samples were processed using Gen 2 process comprising...
4549 Background: The HCRN GU16-260 study showed that nivolumab (nivo) monotherapy is active in treatment-naïve patients (pts) with RCC. Although efficacy correlated tumor cell (TC) PD-L1 expression, more clinically relevant biomarkers are needed. We previously levels of CD8+ tumor-infiltrating lymphocytes (TIL) expressing PD-1 but not TIM-3 and LAG-3 (CD8+ PD1+ TIM3- LAG3-) were associated response to nivo treated clear RCC (ccRCC) pts (Pignon, 2019; Ficial, 2021). Here, we sought validate...
68Ga Prostate-specific membrane antigen (PSMA) is an increasingly popular radiopharmaceutical tracer in prostate cancer and becoming researched other cancers such as breast cancer, renal cell carcinoma, glioblastoma multiforme, among others. Cholangiocarcinoma the second most common primary hepatic malignant tumor; it aggressive tumor with a 5-year survival rate of less than 5 %. We herein report case cholangiocarcinoma detected on 68Ga-PSMA PET-CT conducted part follow up for confirmed by...
476 Background: ChRCC is a rare form of kidney cancer with poor prognosis in the metastatic setting, part due to very limited responses immune checkpoint inhibitors (ICIs), as compared clear cell RCC (ccRCC). The mechanisms underlying response ICIs remain largely uncharacterized. We therefore investigated at single-cell resolution cellular and molecular determinants anti-tumor immunity ChRCC. Methods: samples matched normal specimens were evaluated using RNA (scRNA-seq) T-cell receptor...
449 Background: Sarcomatoid differentiation (SD) in renal cell carcinoma (RCC) is associated with poor survival and heightened response to immune checkpoint blockade. Detection of SD can be challenging due spatial heterogeneity sampling error. Herein, we introduce a novel tissue–informed epigenomic approach noninvasively identify sarcomatoid patients RCC from cell-free DNA (cfDNA) using <1mL plasma. Methods: Methylated immunoprecipitation high-throughput sequencing (MeDIP-seq) was...
448 Background: There is evidence that intratumoral myeloid cell infiltration can modulate response to immune checkpoint inhibitors in some tumor types, but its role ccRCC remains unclear. Here, we investigated the of tumor-infiltrating CD163-positive macrophages as a determinant clinical outcome anti-PD-1 therapy patients (pts) with advanced treated first-line nivolumab part HCRN GU16-260 trial. Methods: Primary tissues from pts (n= 67) were analyzed by multiparametric immunofluorescence...
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<div>AbstractPurpose:<p>Programmed cell death protein 1 (PD-1) expression on CD8<sup>+</sup>TIM-3<sup>−</sup>LAG-3<sup>−</sup> tumor-infiltrating cells predicts positive response to PD-1 blockade in metastatic clear-cell renal carcinoma (mccRCC). Because inhibition of signaling regulatory T (Treg) augments their immunosuppressive function, we hypothesized that Tregs would predict resistance inhibitors.</p>Experimental...
<p>Supplementary Methods</p>
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