A5043493625- Cancer Immunotherapy and Biomarkers
- Genetic factors in colorectal cancer
- Sarcoma Diagnosis and Treatment
- Colorectal Cancer Treatments and Studies
- CAR-T cell therapy research
- Immunotherapy and Immune Responses
- Immune Cell Function and Interaction
- Lymphoma Diagnosis and Treatment
- Neuroblastoma Research and Treatments
- Hematopoietic Stem Cell Transplantation
- Neurofibromatosis and Schwannoma Cases
- Immune cells in cancer
- Colorectal Cancer Surgical Treatments
- Cancer Research and Treatments
- Cancer Mechanisms and Therapy
- Microscopic Colitis
- Gut microbiota and health
- Mycobacterium research and diagnosis
- Cancer Cells and Metastasis
- Cancer Genomics and Diagnostics
- Nerve injury and regeneration
- Ferroptosis and cancer prognosis
- Polyomavirus and related diseases
- Cytokine Signaling Pathways and Interactions
- Colorectal and Anal Carcinomas
Johns Hopkins University
2015-2024
Bloomberg (United States)
2017-2024
Sidney Kimmel Comprehensive Cancer Center
2014-2024
Johns Hopkins Medicine
2014-2024
University of Baltimore
2015-2024
Pediatrics and Genetics
2022
Sidney Kimmel Cancer Center
2019
Johns Hopkins Hospital
2016-2017
Harvard University
2003-2011
Brigham and Women's Hospital
2004-2011
We examined the immune microenvironment of primary colorectal cancer using immunohistochemistry, laser capture microdissection/qRT-PCR, flow cytometry, and functional analysis tumor-infiltrating lymphocytes. A subset displayed high infiltration with activated CD8(+) cytotoxic T lymphocyte (CTL) as well Th1 cells characterized by IFNγ production transcription factor TBET. Parallel tumor genotypes revealed that virtually all tumors this active Th1/CTL had defects in mismatch repair, evidenced...
Significance We demonstrate, to our knowledge for the first time, that bacterial biofilms are associated with colorectal cancers, one of leading malignancies in United States and abroad. Colon biofilms, dense communities bacteria encased a likely complex matrix contact colon epithelial cells, nearly universal on right tumors. Most remarkably, biofilm presence correlates tissue invasion changes biology enhanced cellular proliferation, basic feature oncogenic transformation occurring even...
IL17-producing Th17 cells, generated through a STAT3-dependent mechanism, have been shown to promote carcinogenesis in many systems, including microbe-driven colon cancer. Additional sources of IL17, such as γδ T become available under inflammatory conditions, but their contributions cancer development are unclear. In this study, we modeled Th17-driven tumorigenesis by colonizing Min(Ap) (c+/-) mice with the human gut bacterium, enterotoxigenic Bacteroides fragilis (ETBF), investigate link...
Background Current therapy for osteosarcoma pulmonary metastases (PMs) is ineffective. The mechanisms that prevent successful immunotherapy in are incompletely understood. We investigated the tumor microenvironment of metastatic with goal harnessing immune system as a therapeutic strategy. Methods 66 tissue specimens were analyzed by immunohistochemistry (IHC) and markers digitally quantified. Tumor-infiltrating lymphocytes (TILs) from 25 profiled functional cytometry. Comparative...
ABSTRACT Pseudomonas aeruginosa is a serious pathogen in hospitalized, immunocompromised, and cystic fibrosis (CF) patients. P. motile via single polar flagellum made of polymerized flagellin proteins differentiated into two major serotypes: b. Antibodies to flagella delay onset infection CF patients, but whether immunity polymeric that monomeric are comparable has not been addressed, nor the question such antibodies might negatively impact Toll-like receptor 5 (TLR5) activation, an...
Allogeneic hematopoietic stem cell transplantation (HSCT) is curative for many nonmalignant pediatric disorders, including hemoglobinopathies, bone marrow failure syndromes, and immunodeficiencies. There great success using HLA-matched related donors these patients; however, the use of alternative has been associated with increased graft failure, graft-versus-host disease (GVHD), transplant-related mortality (TRM). HSCT post-transplantation cyclophosphamide (PT/Cy) GVHD prophylaxis performed...
Even though virtually all patients with Ewing sarcoma achieve a radiographic complete response, up to 30% of who present localized disease and 90% those metastases experience metastatic recurrence, highlighting the inability identify residual at end therapy. Up 95% sarcomas carry driving EWS-ETS translocation that has an intronic breakpoint is specific each tumor, authors developed system quantitatively detect DNA fragment in patient plasma.The used long-range multiplex polymerase chain...
Lower-intensity conditioning regimens for haploidentical blood or marrow transplantation (BMT) are safe and efficacious adult patients with hematologic malignancies. We report data pediatric/young high-risk malignancies (n = 40) treated nonmyeloablative BMT post-transplantation cyclophosphamide from 2003 to 2015. Patients received a preparative regimen of fludarabine, cyclophosphamide, total body irradiation. Post-transplantation immunosuppression consisted mycophenolate mofetil, tacrolimus....
Abstract Promising results have been reported for patients with high-risk hematologic malignancies undergoing HLA-haploidentical bone marrow transplantation (haploBMT) posttransplantation cyclophosphamide (PTCy), but there are few data on outcomes myeloablative conditioning in this context. We report the of a single-institution, prospective phase 2 trial haploBMT using busulfan-based or total body irradiation–based 96 children adults (median age, 42 years; range, 1-65 years) malignancies....
Approximately 10% of patients with mismatch repair-proficient (MMRp) colorectal cancer showed clinical benefit to anti-PD-1 monotherapy (NCT01876511). We sought identify biomarkers that delineate immunoreactive and explore new combinatorial immunotherapy strategies can impact MMRp cancer.
Clinical trials with immune checkpoint inhibition in sarcomas have demonstrated minimal response. Here, we interrogated the tumor microenvironment (TME) of two contrasting soft-tissue (STS), rhabdomyosarcomas and undifferentiated pleomorphic (UPS), differing genetic underpinnings responses to understand mechanisms that lead response.Utilizing fresh formalin-fixed, paraffin-embedded tissue from patients diagnosed UPS rhabdomyosarcomas, dissected TME by using IHC, flow cytometry, comparative...
We perform an immunogenomics analysis utilizing whole-transcriptome sequencing of 657 pediatric extracranial solid cancer samples representing 14 diagnoses, and additionally utilize transcriptomes 131 cell lines 147 normal tissue for comparison. describe patterns infiltrating immune cells, T receptor (TCR) clonal expansion, translationally relevant checkpoints. find that tumor-infiltrating lymphocytes TCR counts vary widely across types within each diagnosis, notably are significantly...
Abstract Two fully human mAbs specific for epitopes dependent on intact carboxylate groups the C6 carbon of mannuronic acid components Pseudomonas aeruginosa alginate were found to promote phagocytic killing both mucoid and nonmucoid strains as well protection against types in a mouse model acute pneumonia. The specificity was determined by ELISA assays. Some P. did not make detectable vitro, but vivo lethal pneumonia obtained shown be due rapid induction expression murine lung. No...
Several predictive biomarkers are currently approved or under investigation for the selection of patients checkpoint blockade. Tumor PD-L1 expression is used stratification non-small cell lung (NSCLC) patients, with tumor mutational burden (TMB) also being explored promising results, and mismatch-repair deficiency site-agnostic disease. While tumors high expression, TMB, mismatch repair respond well to blockade, lower burdens, proficiency much less frequently.We studied two unexpected...
New biological insights are increasingly dependent upon a deeper understanding of tissue architectures. Critical to such studies spatial transcriptomics technologies, especially those amenable analysis the most widely available human type, formalin-fixed and paraffin-embedded (FFPE) clinical specimens. Here we build on our previous oligonucleotide probe ligation-based approach accurately analyze FFPE mRNA, which suffers from variable levels degradation. Ligation In Situ Hybridization...
ABSTRACT Deterioration of lung function in patients with cystic fibrosis (CF) is closely associated chronic pulmonary infection mucoid Pseudomonas aeruginosa . The exopolysaccharide (MEP) from P. has been shown to induce opsonic antibodies mice that are protective against this infection. MEP-specific also commonly found the sera older CF lacking detectable When used a human vaccine trial, however, MEP only minimally induced antibodies. To evaluate whether conjugation carrier protein could...
ABSTRACT Vaccines that could effectively prevent Pseudomonas aeruginosa pulmonary infections in the settings of cystic fibrosis (CF) and nosocomial pneumonia be exceedingly useful, but to date no effective immunotherapy targeting this pathogen has been successfully developed for routine use humans. Evaluations using animals limited human trials vaccines their associated immune effectors against different P. antigens have suggested antibody conserved surface polysaccharide alginate, as well...
Mismatch-repair deficiency in solid tumors predicts their response to PD-1 blockade. Based on this principle, pembrolizumab is approved as standard of care for patients with unresectable or metastatic microsatellite instability-high (MSI-H) cancer. Despite success, a large majority colorectal cancer are not MSI-H and do benefit from checkpoint blockade treatment. Predictive biomarkers develop personalized medicines guide clinical trials needed these patients. We, therefore, asked whether...
Malignant peripheral nerve sheath tumors (MPNSTs) are highly aggressive soft tissue sarcomas with limited treatment options, and new effective therapeutic strategies desperately needed. We observe antiproliferative potency of genetic depletion PTPN11 or pharmacological inhibition using the SHP2 inhibitor (SHP2i) TNO155. Our studies into signaling response to SHP2i reveal that resistance TNO155 is partially mediated by reduced RB function, we therefore test addition a CDK4/6 (CDK4/6i) enhance...
High-dose cyclophosphamide given after HLA-matched related and unrelated allogeneic bone marrow transplantation (BMT) for patients with hematologic malignancies is effective single-agent graft-versus-host disease (GVHD) prophylaxis in adults. Data describing outcomes pediatric young adult have not been reported. Between the years 2007 2013, 29 ages ≤21 of age treated at our institution high-risk underwent myeloablative T cell-replete BMT. Eleven received post-transplantation (PTCy) as GVHD...
Fibrolamellar carcinoma (FLC) is a rare type of liver cancer that affects adolescents and young adults. The most effective treatment for FLC surgical resection, but no standardized systemic therapy exists patients with recurrent or unresectable FLC. As first step to understand the immune microenvironment FLC, we investigated targetable immune-checkpoint pathways, PD-1, PD-L1, B7-H3, IDO-1, LAG3, in relation CD8+ cytotoxic T-lymphocyte density. Thirty-two tumor specimens were analyzed using...
Abstract Purpose CIC -rearranged sarcomas represent a type of undifferentiated small round cell sarcoma (USRCS) characterized by poor survival, rapid development chemotherapy resistance, and high rates metastasis. We aim to contribute the growing body knowledge regarding diagnosis, treatment, clinical course, outcomes for these patients. Methods This case series investigates courses ten patients with treated at Johns Hopkins Hospital from July 2014 through January 2024. Clinical data were...
Brain metastases in pediatric osteosarcoma are infrequent but associated with a dire prognosis.