A5087859996- Cancer Immunotherapy and Biomarkers
- CAR-T cell therapy research
- Cutaneous Melanoma Detection and Management
- Immunotherapy and Immune Responses
- Nonmelanoma Skin Cancer Studies
- Melanoma and MAPK Pathways
- Reconstructive Surgery and Microvascular Techniques
- Immune Cell Function and Interaction
- Cell death mechanisms and regulation
- Organ and Tissue Transplantation Research
- Reconstructive Facial Surgery Techniques
- Polyomavirus and related diseases
- SARS-CoV-2 and COVID-19 Research
- Immune cells in cancer
- Cancer Genomics and Diagnostics
- RNA Interference and Gene Delivery
- Virus-based gene therapy research
- Biosimilars and Bioanalytical Methods
- Cancer and Skin Lesions
- Head and Neck Surgical Oncology
- Cutaneous lymphoproliferative disorders research
- Cancer Research and Treatments
- NF-κB Signaling Pathways
- vaccines and immunoinformatics approaches
- Full-Duplex Wireless Communications
Cleveland Clinic
2016-2025
Theravance Biopharma (United States)
2023-2025
Citigroup
2024
Cleveland Clinic Lerner College of Medicine
2012-2024
Creative Commons
2016-2023
Cleveland Foundation
2017-2023
Case Western Reserve University
2017-2023
University Hospitals Seidman Cancer Center
2016-2021
MetroHealth Medical Center
2021
Cancer Institute (WIA)
2018-2021
The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Cutaneous melanoma have been significantly revised over the past few years response to emerging data on immune checkpoint inhibitor therapies and BRAF-targeted therapy. This article summarizes rationale supporting extensive changes recommendations systemic therapy as adjuvant treatment of resected disease unresectable or distant metastatic disease.
This selection from the NCCN Guidelines for Merkel Cell Carcinoma (MCC) focuses on areas impacted by recently emerging data, including sections describing MCC risk factors, diagnosis, workup, follow-up, and management of advanced disease with radiation systemic therapy. Included in these are discussion new recommendations use cell polyomavirus as a biomarker checkpoint immunotherapies to treat metastatic or unresectable disease. The next update complete version will include more detailed...
Over the past few years, NCCN Guidelines for Melanoma: Cutaneous have been expanded to include pathways treatment of microscopic satellitosis (added in v2.2020), and following Principles sections: Molecular Testing v2.2019), Systemic Therapy Considerations Brain Metastases Management v3.2020). The v1.2021 update included additional modifications these sections notable revisions of: Pathology, Surgical Margins Wide Excision Primary Melanoma, Sentinel Lymph Node Biopsy, Completion/Therapeutic...
Although IL-17 is emerging as an important cytokine in cancer promotion and progression, the underlining molecular mechanism remains unclear. Previous studies suggest that (IL-17A) sustains a chronic inflammatory microenvironment favors tumor formation. Here we report novel IL-17–mediated cascade via IL-17R–Act1–TRAF4–MEKK3–ERK5 positive circuit directly stimulates keratinocyte proliferation this axis dictates expression of target genes Steap4 (a metalloreductase for cell metabolism...
Abstract Patients with resected stage IIB/C melanoma have high recurrence risk, similar to those IIIA/B disease. The phase 3, double-blind CheckMate 76K trial assessed 790 patients randomized 2:1 (stratified by tumor category) nivolumab 480 mg or placebo every 4 weeks for 12 months. primary endpoint was investigator-assessed recurrence-free survival (RFS). Secondary endpoints included distant metastasis-free (DMFS) and safety. At 7.8 months of minimum follow-up, significantly improved RFS...
We have recently reported that tumor-associated lymphocytes obtained from ascitic fluids of women with ovarian carcinoma (OvCA) demonstrate a marked decrease in expression cytoplasmic CD3-zeta and surface CD3-epsilon chains, which is associated altered function T cell receptor (TcR). now OvCAs situ culture express functional Fas ligand (FasL), capable triggering an intrinsic death program Fas-expressing cells. The possibility relationship between TcR was examined. data indicate alterations...
<h3>Background</h3> The suppressive nature of immune cells in the tumor microenvironment plays a major role regulating anti-tumor responses. Our previous work demonstrated that soluble factor from is able to induce suppressor phenotype (SP) human CD8<sup>+</sup> T typified by loss CD27/CD28 expression and acquisition potent function. present study hypothesized mechanism inducing SP are tumor-derived exosomes (TDEs). <h3>Methods</h3> Membrane vesicles TDEs multiple head neck cancer cell...
The expression of CD56, a natural killer cell-associated molecule, on alphabeta T lymphocytes correlates with their increased antitumor effector function. CD56 is also expressed subset gammadelta cells. However, functions CD56(+) cells are poorly characterized.To investigate the potential role in tumor killing, we used isopentenyl pyrophosphate and interleukin-2-expanded from peripheral blood mononuclear healthy donors.Thirty to 70% expanded express surface. Interestingly, although both...
The heterogeneous behavior of patients with melanoma makes prognostication challenging. To address this, a gene expression profile (GEP) test to predict metastatic risk was previously developed. This study evaluates the GEP's prognostic accuracy in an independent cohort cutaneous patients. multi-center analyzed primary tumors from 523 patients, using GEP classify as Class 1 (low risk) and 2 (high risk). Molecular classification correlated clinical outcome assessed along AJCC v7 staging...
BACKGROUND Patients who are chronically immunosuppressed have higher rates of cutaneous squamous cell carcinoma the head and neck (cSCC‐HN). This is largest multi‐institutional study to date investigating effect immune status on disease outcomes in patients with cSCC‐HN underwent surgery received postoperative radiation therapy (RT). METHODS from 3 institutions also RT for primary or recurrent, stage I through IV between 1995 2015 were included this institutional review board‐approved study....
Lrig1 marks a distinct population of stem cells restricted to the upper pilosebaceous unit in normal epidermis. Here we report that IL-17A–mediated activation EGFR plays critical role expansion and migration Lrig1+ their progenies response wounding, thereby promoting wound healing skin tumorigenesis. Lrig1-specific deletion IL-17R adaptor Act1 or mice impairs reduces tumor formation. Mechanistically, recruits for signaling cells. While TRAF4, enriched cells, tethers IL-17RA EGFR, c-Src...
The NCCN Guidelines for Melanoma have been significantly revised over the past few years in response to emerging data on a number of novel agents and treatment regimens. These Insights summarize rationale supporting extensive changes recommendations systemic therapy patients with metastatic or unresectable melanoma.
Talimogene Laherparepvec (T-VEC) is an oncolytic virus approved as intratumoral therapy for treating unresectable stage IIIB-IV metastatic melanoma. The mechanisms of action T-VEC and checkpoint inhibitor are highly complementary. Recent studies have shown that combining with injection can lead to improved response rates melanoma patients.We reviewed 10 consecutive cases IIIC IVM1b patients received plus inhibitor(s) (pembrolizumab, ipilimumab/nivolumab, or nivolumab) treated between June...
A substantial number of patients who relapse and die from cutaneous melanoma (CM) are categorized as being at low risk by traditional staging factors. The 31-gene expression profile (31-GEP) test independently stratifies metastatic with CM (Class 1, 1A indicating lowest risk) or high 2,with 2B highest risk).To assess prediction the 31-GEP within 3 low-risk (according to American Joint Committee on Cancer) populations CM: those sentinel lymph node (SLN) negative, stage I IIA tumors, thin (≤1...
We conducted a randomized phase III trial to evaluate whether adjuvant pembrolizumab for one year (647 patients) improved recurrence-free survival (RFS) or overall (OS) in comparison with high-dose IFNα-2b ipilimumab up three years (654 patients), the approved standard-of-care immunotherapies at time of enrollment patients high-risk resected melanoma. At median follow-up 47.5 months, was associated significantly longer RFS than prior [HR, 0.77; 99.62% confidence interval (CI), 0.59-0.99; P =...
Immune checkpoint inhibitor (ICI) therapy continues to revolutionize melanoma treatment, but only a subset of patients respond. Major efforts are underway develop minimally invasive predictive assays ICI response. Using single-cell transcriptomics, we discovered unique CD8 T cell blood/tumor-shared subpopulation in with high levels oxidative phosphorylation (OXPHOS), the ectonucleotidases CD38 and CD39, both exhaustion cytotoxicity markers. We called this population OXPHOS “CD8+ TOXPHOS...
Immune checkpoint blockade is a promising approach to activate antitumor immunity and improve the survival of patients with cancer. V-domain immunoglobulin suppressor T cell activation (VISTA) an immune target; however, downstream signaling mechanisms are elusive. Here, we identify leucine-rich repeats immunoglobulin-like domains 1 (LRIG1) as VISTA binding partner, which acts inhibitory receptor by engaging suppressing pathways. Mice cell-specific LRIG1 deletion developed superior responses...
Abstract Senescent and suppressor T cells are reported to be increased in select patients with cancer poor prognostic indicators. Based on the association of these outcomes, we hypothesized that tumors induce senescence cells, which negatively effects antitumor immunity. In this report, show human from healthy donors incubated tumor for only 6 h at a low T-cell ratio undergo senescence-like phenotype, characterized by loss CD27 CD28 expression telomere shortening. Tumor-induced is induced...