A5012223543- Lung Cancer Treatments and Mutations
- RNA modifications and cancer
- Cancer Genomics and Diagnostics
- Cancer Immunotherapy and Biomarkers
- Lung Cancer Research Studies
- Radiomics and Machine Learning in Medical Imaging
- Lung Cancer Diagnosis and Treatment
- Ferroptosis and cancer prognosis
- Vector-borne infectious diseases
- Viral Infections and Vectors
- Cancer-related molecular mechanisms research
- Peptidase Inhibition and Analysis
- Cholangiocarcinoma and Gallbladder Cancer Studies
- AI in cancer detection
- Toxin Mechanisms and Immunotoxins
- Pancreatic and Hepatic Oncology Research
- Nanoplatforms for cancer theranostics
- Bladder and Urothelial Cancer Treatments
- Colorectal Cancer Treatments and Studies
- Insect Resistance and Genetics
- Autoimmune and Inflammatory Disorders Research
- Lymphoma Diagnosis and Treatment
- Advanced Biosensing Techniques and Applications
- Urinary and Genital Oncology Studies
- DNA Repair Mechanisms
Dana-Farber Brigham Cancer Center
2021-2025
Brigham and Women's Hospital
2020-2025
Dana-Farber Cancer Institute
2021-2025
Tufts University
2019-2022
Tufts Medical Center
2018
Northeastern University
2015-2016
The University of Texas at Tyler
2015
Importance Although tumor mutation burden (TMB) has been explored as a potential biomarker of immunotherapy efficacy in solid tumors, there still is lack consensus about the optimal TMB threshold that best discriminates improved outcomes immune checkpoint inhibitor therapy among patients with non–small cell lung cancer (NSCLC). Objectives To determine association between increasing levels and across clinically relevant programmed death ligand–1 (PD-L1) NSCLC. Design, Setting, Participants...
ABSTRACT Borrelia burgdorferi is the causative agent of Lyme disease, which affects an estimated 300,000 people annually in United States. When treated early, disease usually resolves, but when left untreated, it can result symptoms such as arthritis and encephalopathy. Treatment late-stage may require multiple courses antibiotic therapy. Given that resistance has not been observed for B. , reason recalcitrance to antibiotics unclear. In other chronic infections, presence drug-tolerant...
An elevated peripheral blood derived neutrophil-to-lymphocyte ratio (dNLR) is a negative prognostic marker for patients with non-small cell lung cancer (NSCLC) receiving chemotherapy and immune checkpoint inhibitors. Whether dNLR also associated clinical outcomes to first-line pembrolizumab among NSCLC programmed death ligand 1 (PD-L1) Tumor Proportion Score (TPS) of ≥50% uncertain. How relates the tumor microenvironment unclear.In two participating academic centers, we retrospectively...
Abstract A growing global health concern, Lyme disease has become the most common tick-borne in United States and Europe. Caused by bacterial spirochete Borrelia burgdorferi sensu lato (sl), this can be debilitating if not treated promptly. Because diagnosis is challenging, prevention remains a priority; however, previously licensed vaccine no longer available to public. Here, we designed six component that elicits antibody (Ab) responses against all strains commonly cause humans. The outer...
Clear cell renal carcinoma (ccRCC) is molecularly heterogeneous, immune infiltrated, and selectively sensitive to checkpoint inhibition (ICI). However, the joint tumor-immune states that mediate ICI response remain elusive. We develop spatially aware deep-learning models of tumor features learn representations ccRCC tumors using diagnostic whole-slide images (WSIs) in untreated treated contexts (n = 1,102 patients). identify patterns grade heterogeneity WSIs not achievable through human...
Borrelia burgdorferi, the causative agent of Lyme disease in humans, is maintained a complex biphasic life cycle, which alternates between tick and vertebrate hosts. To successfully survive complete its enzootic B. burgdorferi adapts to diverse hosts by regulating genes required for survival specific environments. Here we describe first ever use transposon insertion sequencing (Tn-seq) identify host. We found that insertions into 46 resulted loss recovery mutants from larval Ixodes ticks....
Ataxia-telangiectasia mutated (ATM) plays a central role in the cellular response to DNA damage and ATM alterations are common several tumor types including bladder cancer. However, specific impact of on therapy cancer is uncertain. Here, we combine preclinical modeling clinical analyses comprehensively define We show that loss sufficient increase sensitivity DNA-damaging agents cisplatin radiation. Furthermore, drives repair–targeted poly(ADP-ribose) polymerase (PARP) Ataxia telangiectasia...
Abstract Purpose: ATM is the most commonly mutated DNA damage and repair gene in non–small cell lung cancer (NSCLC); however, limited characterization has been pursued. Experimental Design: Clinicopathologic, genomic, treatment data were collected for 5,172 patients with NSCLC tumors which underwent genomic profiling. IHC was performed on 182 NSCLCs mutations. Multiplexed immunofluorescence a subset of 535 samples to examine tumor-infiltrating immune subsets. Results: A total 562 deleterious...
BackgroundNon-small cell lung cancer (NSCLC) patients aged ≥80 years [y] are underrepresented in clinical trials. We evaluated whether age correlates with a distinct immunophenotype or impacts outcomes to first-line pembrolizumab advanced NSCLC, PD-L1 Tumor Proportion Score (TPS) of ≥50%, and ≥80y.MethodsThree NSCLC cohorts were retrospectively analyzed assess the impact (<80y versus ≥80y) on efficacy tumor microenvironment (TME). Cohort A encompassed receiving for ≥50%. B comprised...
Deciphering the composition and spatial organization of tumor immune microenvironment (TiME) is key to uncovering mechanisms driving cancer progression treatment response. Spatial biology techniques like multiplex immunofluorescence (mIF) offer detailed insights into TiME but are often limited retrospective research studies individual types. Conversely, bulk omics have been studied in pan-cancer settings fail capture single-cell information. Here, we provide a characterization biomarkers...
Borrelia burgdorferi is the causative agent of Lyme borreliosis. Antibiotic therapy early acute infection effective for most patients, but 10 to 20% go on develop posttreatment disease syndrome (PTLDS). The nature PTLDS remains unknown, currently approved antibiotics treatment do not appear impact these symptoms after they have developed. We reason that minimizing time pathogen interacts with host will diminish probability developing PTLDS, irrespective its nature. This calls an efficient...
9043 Background: Although 1 st -line PD-1 monotherapy has improved survival in advanced NSCLC with a PD-L1 TPS ≥50%, responses occur ̃45% of patients (pts). We previously showed that among pts treated pembrolizumab, clinical outcomes were significantly those ≥90% compared to 50-89%. Here, we report the 3-year analysis pembrolizumab vs 50-89%, and characterize genomic immunophenotypic differences between these expression groups. Methods: Pts stage IV EGFR/ALK wild-type ≥50% who received at...
Clear cell renal carcinoma (ccRCC) is molecularly heterogeneous, immune infiltrated, and selectively sensitive to checkpoint inhibition (ICI). Established histopathology paradigms like nuclear grade have baseline prognostic relevance for ccRCC, although whether existing or novel histologic features encode additional heterogeneous biological clinical states in ccRCC uncertain. Here, we developed spatially aware deep learning models of tumor- immune-related learn representations tumors using...
Abstract Unrecognized immunodeficiency has been proposed as a possible cause of failure antibiotics to resolve symptoms Lyme disease. Here, we examined the efficacy doxycycline in different immunodeficient mice identify defects that impair antibiotic treatment outcomes. We found had significantly lower absence adaptive immunity, specifically B cells. This effect was most pronounced C3H compared with C57BL/6 mice, suggesting role for genetic background beyond immunodeficiency. Addition single...
<div>Abstract<p>Introduction: <i>ATM</i> is the most commonly mutated DNA damage and repair gene in non-small cell lung cancer (NSCLC), however limited characterization has been pursued. Methods: Clinicopathologic, genomic, treatment data were collected for 5172 patients with NSCLC tumors which underwent genomic profiling. ATM immunohistochemistry (IHC) was performed on 182 NSCLCs mutations. Multiplexed immunofluorescence a subset of 535 samples to examine...
<p>Supplementary Figure 10. (A) Progression-free and (B) overall survival among all patients with stage III NSCLC according to ATM mutation status. (C) (D) who received concurrent chemoradiotherapy followed by durvalumab maintenance status.</p>
<p>Supplementary Figure 14. (A) Objective response rate, (B) progression-free survival, and (C) overall survival to PD-(L)1 immune checkpoint blockade monotherapy among patients with advanced/metastatic PD-L1 negative (<1%) NSCLC, according ATM mutation status. (D) (E) (F) intermediate (1-49%) (G) (H) (I) high (≥50%) status.</p>
<p>Supplementary Figure 23. Correlation of intratumoral, tumor-stroma interface, and total CD8+, PD1+, CD8+PD1+, FOXP3+ T cells tumoral non-tumoral PD-L1+ among ATMMUT NSCLCs.</p>
<p>Supplementary Figure 16. (A) Objective response rate, (B) progression-free survival, and (C) overall survival to PD-(L)1 inhibition monotherapy among patients with advanced/metastatic NSCLC, according ATM/TP53 co-mutation status. (D) (E) (F) in combination chemotherapy advanced status.</p>