A5010958654- Melanoma and MAPK Pathways
- Cancer Immunotherapy and Biomarkers
- CAR-T cell therapy research
- Immunotherapy and Immune Responses
- Chemokine receptors and signaling
- Synthesis and biological activity
- Peptidase Inhibition and Analysis
- T-cell and B-cell Immunology
- Cancer Mechanisms and Therapy
- melanin and skin pigmentation
- Immune cells in cancer
- Immune Cell Function and Interaction
- Cutaneous Melanoma Detection and Management
- Nanoplatforms for cancer theranostics
- Lung Cancer Research Studies
- Cell Adhesion Molecules Research
- Neuroendocrine Tumor Research Advances
- Cytokine Signaling Pathways and Interactions
- Lung Cancer Treatments and Mutations
- Cancer Genomics and Diagnostics
- Receptor Mechanisms and Signaling
- Advanced Breast Cancer Therapies
- Atherosclerosis and Cardiovascular Diseases
- Click Chemistry and Applications
- Lymphoma Diagnosis and Treatment
Dartmouth College
2011-2018
Falmouth Hospital
2016
Dartmouth–Hitchcock Medical Center
2014-2015
Dartmouth Hospital
2011-2013
National Institutes of Health
1994-2013
Center for Cancer Research
2008
National Cancer Institute
1988-2008
Science Applications International Corporation (United States)
2007
Comcast (United States)
2007
Columbia University
1991-2004
Tissue-resident memory T (TRM) cells have been widely characterized in infectious disease settings; however, their role mediating immunity to cancer remains unknown. We report that skin-resident cell responses melanoma are generated naturally as a result of autoimmune vitiligo. Melanoma antigen-specific TRM resided predominantly melanocyte-depleted hair follicles and were maintained without recirculation or replenishment from the lymphoid compartment. These expressed CD103, CD69, CLA...
To correlate in vitro characteristics of tumor-infiltrating lymphocytes (TIL) with clinical response to TIL immunotherapy patients metastatic melanoma.Forty-one melanoma undergoing 43 separate treatment courses and interleukin-2 (IL-2) from December 1990 through November 1992 were studied prospectively. Multiple patient evaluated for correlates. In addition, assayed within 7 days infusion such as doubling time, cell-surface phenotype, autologous tumor lysis 4-hour chromium-51 release assays,...
Abstract Acquired resistance to BRAFV600E inhibitors (BRAFi) in melanoma remains a common clinical obstacle, as is the case for any targeted drug therapy that can be developed given plastic nature of cancers. Although there has been significant focus on cancer cell-intrinsic properties BRAFi resistance, impact host immunity not explored. Here we provide preclinical evidence an autochthonous mouse model associated with restoration myeloid-derived suppressor cells (MDSC) tumor...
Rates of melanoma are steadily on the rise, with a current lifetime incidence 1 in 50 individuals (Balch et al., 2004; Smalley 2005). In nearly 50% human melanomas, BRAF oncogene encodes BRAFV600E (Lee 2011; Long Menzies 2012; Rubinstein 2010), protein whose expression increases progression via activation signaling cascades and downstream genes (Chapman Joseph 2010; Koya Vultur Yang 2010). Vemurafenib, also known as PLX4032, is small molecule inhibitor that binds to ATP-binding site mutated...
Regulatory T cells (Treg) are critical mediators of immunosuppression in established tumors, although little is known about their role restraining immunosurveillance during tumorigenesis. Here, we employ an inducible autochthonous model melanoma to investigate the earliest Treg and CD8 effector T-cell responses oncogene-driven Induction oncogenic BRAFV600E loss Pten melanocytes led localized accumulation FoxP3+ Tregs, but not cells, within 1 week detectable increases melanocyte...
A growing body of evidence suggests that BRAF inhibitors, in addition to their acute tumor growth-inhibitory effects, can also promote immune responses melanoma. The present study aimed define the immunologic basis BRAF-inhibitor therapy using Braf/Pten model inducible, autochthonous melanoma on a pure C57BL/6 background. In microenvironment, inhibitor PLX4720 functioned by on-target mechanisms selectively decrease both proportions and absolute numbers CD4(+)Foxp3(+) regulatory T cells...
<h3>Background:</h3> Autosomal recessive congenital ichthyosis (ARCI) is a rare hereditary disorder of cornification. Mutations in the transglutaminase-1 (<i>TGM1</i>) gene, which encodes for epidermal enzyme (TGase-1), are one causes ARCI. <h3>Methods:</h3> The <i>TGM1</i> mutation spectrum was characterised and genotype–phenotype correlations investigated 104 patients with ARCI ascertained through National Registry Ichthyosis Related Disorders USA. Germline mutations were identified 55%...
A link between autoimmunity and improved antitumor immunity has long been recognized, although the exact mechanistic relationship these two phenomena remains unclear. In present study we have found that vitiligo, autoimmune destruction of melanocytes, generates self antigen required for mounting persistent protective memory CD8+ T cell responses to melanoma. Vitiligo developed in approximately 60% mice were depleted regulatory CD4+ cells then subjected surgical excision large established B16...
Obese individuals have altered pharmacokinetics for many medications when compared with the non-obese. For oncologist treating an obese cancer patient, these changes in drug disposition may potentially cause increased therapy-related toxicity. As a consequence, oncologists frequently treat patients dose reductions effort to decrease chemotherapy However, little clinical data exist either support or refute this policy. The course of cohort treated small-cell lung (SCLC) was evaluated...
10001 Background: ASPS accounts for < 1% of soft tissue sarcomas. is associated with the t(X;17)(p11;q25) translocation, ASPL-TFE3 fusion protein. There no effective systemic treatment metastatic ASPS. Cediranib (C) a potent oral inhibitor vascular endothelial growth factor receptor (VEGFR-1,-2,-3) tyrosine kinases. Methods: Phase II trial to determine response rate (PR + CR) patients (pts) C; assess effect C on tumor angiogenesis using DCE-MRI and proliferation FDG-PET; compare gene...
Background We have previously demonstrated that temporary depletion of CD4 T cells in mice with progressive B16 melanoma, followed by surgical tumor excision, induces protective memory CD8 cell responses to melanoma/melanocyte antigens. also showed persistence these is supported, an antigen-dependent fashion, concurrent autoimmune melanocyte destruction. Herein we explore the requirement help priming and maintaining this response melanoma. Methodology Principal Findings To induce...
Abstract Vitiligo is a CD8 T cell–mediated autoimmune disease that has been shown to promote the longevity of memory cell responses melanoma. However, mechanisms whereby melanocyte/melanoma Ag-specific are perpetuated in context vitiligo not well understood. These studies investigate possible phenomenon naive priming hosts with melanoma-initiated, self-perpetuating, vitiligo. Using pmel (gp10025–33–specific) transgenic cells, we demonstrate melanocyte destruction induces proliferation...
As BRAFV600E-inhibitors become standard treatment for many metastatic melanoma patients, research has begun to elucidate their impact on the tumor immune landscape. Here, we highlight our recent studies demonstrating ability of cell-intrinsic BRAFV600E-inhibition selectively reduce intratumoral immunosuppressive cell populations and enhance antitumor CD8+ T-cell immunity.
10565 Background: DNA double-strand breaks (DSBs) caused by exposure to damaging agents initiate phosphorylation of histone H2AX form gamma-H2AX, which is considered a surrogate marker DSBs. However, it challenge quantitatively measure gamma-H2AX in clinical samples such as tumor biopsies. The aim this study was develop an immunohistochemical detection method for and evaluate the levels paraffin-embedded samples. Methods: Human breast cancer MCF-7 cells were treated with topoisomerase I...