Kelly P. Burke
A5055536350- Cancer Immunotherapy and Biomarkers
- CAR-T cell therapy research
- Cancer Genomics and Diagnostics
- Pancreatic and Hepatic Oncology Research
- Renal cell carcinoma treatment
- Immunotherapy and Immune Responses
- Immune Cell Function and Interaction
- Hepatitis C virus research
- Single-cell and spatial transcriptomics
- T-cell and B-cell Immunology
- Immune cells in cancer
- HIV Research and Treatment
- Monoclonal and Polyclonal Antibodies Research
- vaccines and immunoinformatics approaches
- Genetics, Bioinformatics, and Biomedical Research
- Hepatitis B Virus Studies
- Prostate Cancer Treatment and Research
- Epigenetics and DNA Methylation
- Biomedical and Engineering Education
- Radiomics and Machine Learning in Medical Imaging
- Genetic factors in colorectal cancer
- Melanoma and MAPK Pathways
- Cancer Cells and Metastasis
- Mercury impact and mitigation studies
- RNA regulation and disease
Dana-Farber Cancer Institute
2016-2025
Harvard University
2016-2024
Boston VA Research Institute
2020-2024
Brigham and Women's Hospital
2018-2024
Broad Institute
2023-2024
Massachusetts Institute of Technology
2024
Massachusetts General Hospital
2024
Johns Hopkins University
2010-2012
Office of Infectious Diseases
2012
Columbia University
2011
Clinically relevant subtypes exist for pancreatic ductal adenocarcinoma (PDAC), but molecular characterization is not yet standard in clinical care. We implemented a biopsy protocol to perform time-sensitive whole-exome sequencing and RNA patients with advanced PDAC. Therapeutically genomic alterations were identified 48% (34/71) pathogenic/likely pathogenic germline 18% (13/71) of patients. Overall, 30% (21/71) enrolled experienced change management as result data. Twenty-six had and/or...
BACKGROUND. Understanding the integrated immunogenomic landscape of advanced prostate cancer (APC) could impact stratified treatment selection.
Abstract Metastatic castration-resistant prostate cancer is typically lethal, exhibiting intrinsic or acquired resistance to second-generation androgen-targeting therapies and minimal response immune checkpoint inhibitors 1 . Cellular programs driving in both cells remain poorly understood. We present single-cell transcriptomes from 14 patients with advanced cancer, spanning all common metastatic sites. Irrespective of treatment exposure, adenocarcinoma pervasively coexpressed multiple...
Abstract While BRAF inhibitor combinations with EGFR and/or MEK inhibitors have improved clinical efficacy in V600E colorectal cancer (CRC), response rates remain low and lack durability. Preclinical data suggest that BRAF/MAPK pathway inhibition may augment the tumor immune response. We performed a proof-of-concept single-arm phase 2 trial of combined PD-1, sparatlizumab (PDR001), dabrafenib trametinib 37 patients CRC. The primary end point was overall rate, secondary points were...
Trogocytosis modulates immune responses, with still unclear underlying molecular mechanisms. Using leukemia mouse models, we found that lymphocytes perform trogocytosis at high rates tumor cells. While performing trogocytosis, both Natural Killer (NK) and CD8 + T cells acquire the checkpoint receptor PD-1 from In vitro in vivo investigation revealed on surface of NK cells, rather than being endogenously expressed, was derived entirely a SLAM receptor–dependent fashion. acquired via actively...
The ability to monitor anti-tumor CD8+ T cell responses in the blood has tremendous therapeutic potential. Here, we used paired single-cell RNA and TCR sequencing detect characterize "tumor-matching" (TM) cells of mice with MC38 tumors or melanoma patients using as a molecular barcode. TM showed increased activation compared nonmatching were less exhausted than matching tumors. Importantly, PD-1, which been identify putative circulating cells, poor sensitivity for identifying cells. By...
The PD-1 pathway regulates dysfunctional T cells in chronic infection and cancer, but the role of this during acute remains less clear. Here, we demonstrate that signals are needed for optimal memory. Mice deficient exhibit impaired CD8+ cell memory following influenza infection, including reduced virus-specific numbers compromised recall responses. blockade priming leads to similar differences early post-infection without defect formation, suggesting timing and/or duration could be tailored...
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...
Metastasis drives mortality and morbidity in cancer. While some patients develop broad metastatic disease across multiple organs, others exhibit organ-specific spread. To identify mechanisms underlying organotropism, we analyzed clinico-genomic data from over 7,000 with cutaneous melanoma three independent cohorts (one primary discovery two validation including a nationwide electronic health record-derived deidentified database), leveraging machine learning approaches to clinical data. We...
Background: Immune checkpoint blockade (ICB) has revolutionized clinical outcomes in melanoma. Compared with single ICB (aCTLA-4, aPD-1), combination aCTLA-4 plus aPD-1 shows the highest response rate, 50%-60% patients responding to treatment. However, it also toxicity about 50% developing high grade toxicity. Identifying circulating immune cells as biomarkers predict could guide decisions and shed light on potential mechanisms driving Methods: We identified quantified proportions using...
Abstract Vaccines designed to prevent or treat hepatitis C viral infection must achieve maximum cross-reactivity against widely divergent circulating strains. Rational approaches for sequence selection maximize immunogenicity and minimize genetic distance across strains may enhance vaccine induction of optimal cytotoxic T cell responses. We assessed recognition potential virus (HCV) sequences generated using three rational approaches: combining epitopes with predicted tight binding the MHC,...
Background. Combination antiretroviral therapy (cART) reduces genital tract human immunodeficiency virus type 1 (HIV-1) load and the risk of sexual transmission, but little is known about efficacy cART for decreasing viral (GTVL) differences in sex or HIV-1 subtype.
ABSTRACT Hepatitis C virus (HCV) research is hampered by the use of arbitrary representative isolates in cell culture and immunology. The most replicative isolate vitro a subtype 2a (JFH-1); however, genotype 1 more prevalent worldwide represents about 70% infections United States, genotypes differ from one another 31% to 33% at nucleotide level. For phylogenetic immunologic analyses, viruses H77 HCV-1 (both 1a) are commonly used based on their historic importance. In an effort rationally...
Abstract Immune checkpoint inhibitors (ICIs) have heralded a remarkable shift in cancer care, significantly extending survival for advanced patients. However, despite their clinical successes, substantial majority of patients fail to achieve lasting response ICIs. To address this challenge and gain insights into the complex landscape tumor microenvironment (TME), we conducted an extensive analysis using single-cell RNA sequencing (scRNA; ∼216K cells across 39 samples) single-nucleus...
While immune-checkpoint blockade (ICB) has revolutionized treatment of metastatic melanoma over the last decade, identification broadly applicable robust biomarkers been challenging, driven in large part by heterogeneity ICB regimens and patient tumor characteristics. To disentangle these features, we performed a standardized meta-analysis eight cohorts patients treated with anti-PD-1 (n=290), anti-CTLA-4 (n=175), combination anti-PD-1/anti-CTLA-4 (n=51) RNA sequencing pre-treatment clinical...
ABSTRACT Metastatic castration resistant prostate cancer (mCRPC) is primarily treated with therapies that prevent transcriptional activity of the androgen receptor (AR), cause DNA damage, or cell division. Clinical resistance to these therapies, including second-generation androgen-targeting compounds such as enzalutamide and abiraterone, nearly universal. Other treatment modalities, immune checkpoint inhibitors, have provided minimal benefit except in rare subsets patients 1,2 . Both tumour...