A5089680427- Cancer Immunotherapy and Biomarkers
- Immunotherapy and Immune Responses
- CAR-T cell therapy research
- Colorectal Cancer Treatments and Studies
- Lung Cancer Treatments and Mutations
- Cancer Genomics and Diagnostics
- Radiomics and Machine Learning in Medical Imaging
- vaccines and immunoinformatics approaches
- RNA modifications and cancer
- Immune Cell Function and Interaction
- Immune cells in cancer
- Cutaneous Melanoma Detection and Management
- Molecular Biology Techniques and Applications
- Lung Cancer Diagnosis and Treatment
- Peptidase Inhibition and Analysis
- Gene expression and cancer classification
- Lung Cancer Research Studies
- Ferroptosis and cancer prognosis
- Bladder and Urothelial Cancer Treatments
- melanin and skin pigmentation
- Cancer-related molecular mechanisms research
- Advanced Proteomics Techniques and Applications
- Inflammasome and immune disorders
- Chemokine receptors and signaling
- Renal cell carcinoma treatment
Yale University
2021-2025
Uppsala University
2013-2023
Yale Cancer Center
2021-2023
University of New Haven
2023
Science for Life Laboratory
2013-2018
Uppsala University Hospital
2018
Resolving the molecular details of proteome variation in different tissues and organs human body will greatly increase our knowledge biology disease. Here, we present a map tissue based on an integrated omics approach that involves quantitative transcriptomics at organ level, combined with microarray–based immunohistochemistry, to achieve spatial localization proteins down single-cell level. Our tissue-based analysis detected more than 90% putative protein-coding genes. We used this explore...
Global classification of the human proteins with regards to spatial expression patterns across organs and tissues is important for studies biology disease. Here, we used a quantitative transcriptomics analysis (RNA-Seq) classify tissue-specific genes representative set all major combined this antibody-based profiling same tissues. To present data, launch new version Human Protein Atlas that integrates RNA protein data corresponding ∼80% protein-coding access primary both on an individual...
Modeling the cancer transcriptome Recent initiatives such as The Cancer Genome Atlas have mapped genome-wide effect of individual genes on tumor growth. By unraveling genomic alterations in tumors, molecular subtypes cancers been identified, which is improving patient diagnostics and treatment. Uhlen et al. developed a computer-based modeling approach to examine different types nearly 8000 patients. They provide an open-access resource for exploring how expression specific influences...
The testis' function is to produce haploid germ cells necessary for reproduction. Here we have combined a genome-wide transcriptomics analysis with immunohistochemistry-based protein profiling characterize the molecular components of testis. Deep sequencing (RNA-Seq) normal human testicular tissue from seven individuals was performed and compared 26 other types. All 20 050 putative genes were classified into categories based on expression patterns. shows that testis most tissue-specific by...
Abstract Semiquantitative assessment of immune markers by immunohistochemistry (IHC) has significant limitations for describing the diversity response in cancer. Therefore, we evaluated a fluorescence‐based multiplexed immunohistochemical method combination with multispectral imaging system to quantify infiltrates situ environment non‐small‐cell lung cancer (NSCLC). A tissue microarray including 57 NSCLC cases was stained antibodies against CD8, CD20, CD4, FOXP3, CD45RO, and pan‐cytokeratin,...
Cancer testis antigens (CTAs) are of clinical interest as biomarkers and present valuable targets for immunotherapy. To comprehensively characterize the CTA landscape non-small-cell lung cancer (NSCLC), we compared RNAseq data from 199 NSCLC tissues to normal transcriptome 142 samples 32 different organs. Of 232 CTAs currently annotated in Caner Testis Database (CTdatabase), 96 were confirmed NSCLC. obtain an unbiased profile NSCLC, applied stringent criteria on our set defined 90 genes...
Abstract Purpose: PD-1/PD-L1 inhibitors are approved for multiple tumor types. However, resistance poses substantial clinical challenges. Patients and Methods: We conducted a phase I trial of CD40 agonist APX005M (sotigalimab) CSF1R inhibitor cabiralizumab with or without nivolumab using 3+3 dose-escalation design (NCT03502330). were enrolled from June 2018 to April 2019. Eligibility included patients biopsy-proven advanced melanoma, non–small cell lung cancer (NSCLC), renal carcinoma (RCC)...
Anti-vascular endothelial growth factor therapy enhances PD-1 inhibitor activity in preclinical models and has been used to treat perilesional cerebral edema radiation necrosis. We conducted a two-institution phase II trial of bevacizumab pembrolizumab patients with untreated melanoma brain metastasis (MBM) (ClinicalTrials.gov identifier: NCT02681549). Patients were anti-PD-(L)-1-naïve, had ≥one asymptomatic, nonhemorrhagic 5-20 mm MBM, not requiring immediate local or steroids. Thirty-seven...
Tumor-associated macrophages (TAMs) are attractive targets for immunotherapy. Recently, studies in animal models showed that treatment with an anti-TAM antibody directed against the scavenger receptor MARCO resulted suppression of tumor growth and metastatic dissemination. Here we investigated expression relation to other macrophage markers immune pathways a non-small cell lung cancer (NSCLC) cohort (n = 352). MARCO, CD68, CD163, MSR1 programmed death ligand-1 (PD-L1) were analyzed by...
Infiltration of T and B/plasma cells has been linked to NSCLC prognosis, but this not thoroughly investigated in relation the expression programmed death ligand 1 (PD-L1). Here, we determine association lymphocytes PD-L1 with overall survival (OS) two retrospective cohorts operated patients who were treated checkpoint inhibitors targeting 1/PD-L1 axis. Moreover, evaluate how positivity clinicopathologic factors affect prognostic lymphocytes.Cluster differentiation (CD) 3 (CD3)-, CD8-, CD4-,...
Targeting tumor-associated blood vessels to increase immune infiltration may enhance treatment effectiveness, yet limited data exist regarding anti-angiogenesis effects on the tumor microenvironment (TME). We hypothesized that dual targeting of angiogenesis with checkpoints would improve both intracranial and extracranial disease. used subcutaneous left ventricle melanoma models evaluate anti-PD-1/anti-VEGF anti-PD-1/lenvatinib (pan-VEGFR inhibitor) combinations. Cytokine/chemokine profiling...
Melanocortin-1 receptor (MC1R) plays a critical role in human pigmentation and DNA repair mechanisms. MC1R-targeting agents are being investigated clinical trials patients with melanoma, yet large studies investigating the rate degree of MC1R expression primary metastatic melanoma tissue lacking.
Background Desmoplastic melanoma (DM) is a rare subtype characterized by dense fibrous stroma, propensity for local recurrence, and high response rate to programmed cell death protein 1 (PD-1) blockade. Occult sentinel lymph node positivity significantly lower in both pure mixed DM than conventional melanoma, underscoring the need better prognostic biomarkers inform therapeutic strategies. Methods We assembled tissue microarray comprising various cores of tumor, lymphoid aggregates from 45...
Abstract Immune cells of the tumor microenvironment are central but erratic targets for immunotherapy. The aim this study was to characterize novel patterns immune cell infiltration in non‐small lung cancer (NSCLC) relation its molecular and clinicopathologic characteristics. Lymphocytes (CD3+, CD4+, CD8+, CD20+, FOXP3+, CD45RO+), macrophages (CD163+), plasma (CD138+), NK (NKp46+), PD1+, PD‐L1+ were annotated on a tissue microarray including 357 NSCLC cases. Somatic mutations analyzed by...
The antigenic repertoire of tumors is critical for successful anti-cancer immune response and the efficacy immunotherapy. Cancer-testis antigens (CTAs) are targets humoral cellular reactions. We aimed to characterize CTA expression in non-small cell lung cancer (NSCLC) context microenvironment. Of 90 CTAs validated by RNA sequencing, eight (DPEP3, EZHIP, MAGEA4, MAGEB2, MAGEC2, PAGE1, PRAME, TKTL1) were selected immunohistochemical profiling tissues from 328 NSCLC patients. was compared with...
There is an unmet clinical need for better prognostic and diagnostic tools renal cell carcinoma (RCC). Human Protein Atlas data resources, including the transcriptomes proteomes of normal malignant human tissues, were searched RCC-specific proteins cubilin (CUBN) identified as a candidate. Patient tissue representing various cancer types was constructed into microarray (n = 940) immunohistochemistry used to investigate specificity CUBN expression in RCC compared other cancers. Two...
Abstract The adrenal gland is a composite endocrine organ with vital functions that include the synthesis and release of glucocorticoids catecholamines. To define molecular landscape underlies specific gland, we combined genome-wide transcriptomics approach using messenger RNA sequencing human tissues immunohistochemistry-based protein profiling on tissue microarrays. Approximately two-thirds all putative coding genes were expressed in analysis identified 253 an elevated pattern expression...
The cytokine interleukin-18 (IL-18) has immunostimulatory effects but is negatively regulated by a secreted binding protein, IL-18BP, that limits IL-18's anti-cancer efficacy. A "decoy-resistant" form of IL-18 (DR-18), avoids sequestration IL-18BP while maintaining its potential, recently been developed. Here, we investigated the therapeutic potential DR-18 in renal cell carcinoma (RCC). Using pan-tumor transcriptomic data, found clear RCC had among highest expression receptor subunits and...
Background The tumor microenvironment (TME) contributes to cancer progression and treatment response therapy, including in renal cell carcinoma (RCC). Prior profiling studies, single-cell transcriptomics, often involve limited sample sizes lack spatial orientation. TME of RCC brain metastases, a major cause morbidity, also remains largely uncharacterized. Methods We performed digital on the NanoString GeoMx platform using 52 validated immuno-oncology markers tissue microarrays representing...