A5058684304- Cancer Immunotherapy and Biomarkers
- Immunotherapy and Immune Responses
- Cancer Genomics and Diagnostics
- CAR-T cell therapy research
- PARP inhibition in cancer therapy
- Advanced Radiotherapy Techniques
- Head and Neck Cancer Studies
- interferon and immune responses
- Virus-based gene therapy research
- Cervical Cancer and HPV Research
- Lung Cancer Treatments and Mutations
- Immune cells in cancer
- Immune Cell Function and Interaction
- Lung Cancer Research Studies
- Lung Cancer Diagnosis and Treatment
- Artificial Intelligence in Healthcare
- Statistical Methods in Clinical Trials
- Nanoplatforms for cancer theranostics
- Advanced Causal Inference Techniques
- Radiopharmaceutical Chemistry and Applications
- Colorectal and Anal Carcinomas
- Radiomics and Machine Learning in Medical Imaging
- Lymphoma Diagnosis and Treatment
- Neuroblastoma Research and Treatments
- Health Systems, Economic Evaluations, Quality of Life
University of California, San Diego
2016-2025
Moores Cancer Center
2017-2024
Johns Hopkins Medicine
2012-2023
Johns Hopkins University
2012-2023
Precision for Medicine (United States)
2021-2023
Tel Aviv University
2023
University of Nicosia
2023
Sheba Medical Center
2023
La Jolla Alcohol Research
2022
UC San Diego Health System
2022
Purpose: Checkpoint inhibitors demonstrate salutary anticancer effects, including long-term remissions. PD-L1 expression/amplification, high mutational burden, and mismatch repair deficiency correlate with response. We have, however, observed a subset of patients who appear to be "hyperprogressors," greatly accelerated rate tumor growth clinical deterioration compared pretherapy, which was also recently reported by Institut Gustave Roussy. The current study investigated potential genomic...
Abstract The immune-modulating effects of radiotherapy (XRT) have gained considerable interest recently, and there been multiple reports synergy between XRT immunotherapy. However, additional preclinical studies are needed to demonstrate the antigen-specific nature radiation-induced immune responses elucidate potential mechanisms with Here, we ability stereotactic induce endogenous when it is combined anti–PD-1 checkpoint blockade Using small animal radiation research platform (SARRP),...
Trophoblast invasion of the uterine extracellular matrix, a critical process human implantation and essential for fetal development, is striking example controlled invasiveness. To identify molecules that regulate trophoblast invasion, mRNA signatures cells isolated from first trimester (high invasiveness) term placentae (no/low were compared using U95A GeneChip microarrays yielding 220 invasion/migration-related genes. In this 'invasion cluster', KiSS-1 its G-protein-coupled receptor...
Abstract Purpose: In the proper context, radiotherapy can promote antitumor immunity. It is unknown if elective nodal irradiation (ENI), a strategy that irradiates tumor-associated draining lymph nodes (DLN), affects adaptive immune responses and combinatorial efficacy of with checkpoint blockade (ICB). Experimental Design: We developed preclinical model to compare stereotactic (Tumor RT) or without ENI examine immunologic differences between techniques spare irradiate DLN. Results: Tumor RT...
Next-generation sequencing (NGS) can identify novel cancer targets. However, interpreting the molecular findings and accessing drugs/clinical trials is challenging. Furthermore, many tumors show resistance to monotherapies. To implement a precision strategy, we initiated multidisciplinary (basic/translational/clinical investigators, bioinformaticians, geneticists, physicians from multiple specialties) tumor board (MTB), which included project manager facilitate obtaining clinical-grade...
Abstract Purpose: To characterize the role of B cells on human papilloma virus (HPV)-associated cancer patient outcomes and determine effects radiation PD-1 blockade B-cell populations. Experimental Design: Tumor RNA-sequencing data from over 800 patients with head neck squamous cell carcinoma (HNSCC) cervical cancer, including a prospective validation cohort, was analyzed to study impact gene expression overall survival (OS). A novel murine model HPV+ HNSCC used radiotherapy activation,...
Despite the promise of immune checkpoint inhibition (ICI), therapeutic responses remain limited. This raises possibility that standard care treatments delivered in concert may compromise tumor response. To address this, we employ tobacco-signature head and neck squamous cell carcinoma murine models which map tumor-draining lymphatics develop for regional lymphablation with surgery or radiation. We find eliminates ICI response, worsening overall survival repolarizing tumor- peripheral-immune...
Abstract Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer worldwide. Tobacco use main risk factor for HNSCC, tobacco-associated HNSCCs have poor prognosis response to available treatments. Recently approved anti-PD-1 immune checkpoint inhibitors showed limited activity (≤20%) in highlighting need identify new therapeutic options. For this, mouse models that accurately mimic complexity of HNSCC mutational landscape tumor environment are urgently needed. Here, we...
Abstract Neuroendocrine carcinoma of the cervix is an ultra-rare malignancy with a poor prognosis and limited treatment options. Checkpoint blockade immunotherapy has rapidly developed into emerging standard care for several common disease types. Interestingly, in preclinical retrospective clinical data, radiation therapy been demonstrated to synergize checkpoint inhibitors. Here we report patient metastatic, chemotherapy-refractory neuroendocrine who presented partial bowel obstruction due...
The role that human papillomavirus (HPV) oncogenes play in suppressing responses to immunotherapy cancer deserves further investigation. In particular, the effects of HPV E5 remain poorly understood relative E6 and E7. Here, we demonstrate is a negative regulator anti-viral interferon (IFN) response pathways, antigen processing, presentation. Using head neck as model, identify decreases expression function immunoproteasome immunoproteasome, but not constitutive proteasome, associated with...
Processing of the laminin-5 (Ln-5) gamma 2 chain by membrane-type-1 matrix metalloproteinases (MT1-MMP) promotes migration and invasion epithelial tumor cells. We previously demonstrated that MT1-MMP cleaves rat at two sites, producing major C-terminal fragments 100 (gamma 2') 80 x) kDa releasing a 30-kDa fragment containing epidermal growth factor (EGF)-like motifs (domain III (DIII) fragment). The DIII bound EGF receptor (EGF-R) stimulated cell scattering migration. However, it is not yet...
The cGAS-STING cytosolic DNA sensing pathway may play an integral role in the initiation of antitumor immune responses. Studies evaluating immunogenicity various cyclic dinucleotide (CDN) STING agonists administered by intratumoral (i.t.) injection showed potent induction inflammation, tumor necrosis, and, some cases, durable tumor-specific adaptive immunity. However, specific mechanisms underlying these responses remain incompletely defined. majority studies have focused on effect CDNs...
Abstract Higher tumor mutational burden (TMB) has been correlated with response to checkpoint blockade immunotherapy. However, it is unclear whether TMB independently serves as a prognostic biomarker for outcomes in immunotherapy-naïve patients. Here, we evaluated the relationship between and overall survival 1,415 patients diverse advanced malignancies. was studied both tiered variable (low ≤5 mutations/Mb, intermediate >5 <20, high ≥20 <50, very ≥50) continuous...
Abstract Purpose: Human papillomavirus (HPV)-related head and neck squamous cell carcinoma (HNSCC) is associated with daily marijuana use also increasing in parallel increased the United States. Our study designed to define interaction between cannabinoids HPV-positive HNSCC. Experimental Design: The expression of cannabinoid receptors CNR1 CNR2 was analyzed using Cancer Genome Atlas (TCGA) HNSCC data. We used agonists, antagonists, siRNAs, or shRNA-based models explore roles lines animal...
Head and neck squamous cell carcinoma (HNSCC) ranks sixth in cancer incidence worldwide has a 5-year survival rate of only 63%. Immunotherapies-principally immune checkpoint inhibitors (ICI), such as anti-PD-1 anti-CTLA-4 antibodies that restore endogenous antitumor T-cell immunity-offer the greatest promise for HNSCC treatment. Anti-PD-1 been recently approved first-line treatment recurrent metastatic HNSCC; however, less than 20% patients show clinical benefit durable responses. In...
Locally advanced cancers remain therapeutically challenging to eradicate. The most successful treatments continue combine decades old non-targeted chemotherapies with radiotherapy that unfortunately increase normal tissue damage in the irradiated field and have systemic toxicities precluding further treatment intensification. Therefore, alternative molecularly guided therapies are needed improve patient outcomes when applied radiotherapy. In this work, we report a trimodal precision...