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Articles by Tara Mitchell
Five-year survival with neoadjuvant therapy in melanoma: updated pooled analysis from the International Neoadjuvant Melanoma Consortium (INMC)
Abstract Neoadjuvant immune checkpoint inhibitors (ICIs) are standard of care for resectable stage IIIB–D melanoma, but knowledge gaps remain regarding optimal treatment type, long-term survival, postsurgical management and clinical, histopathological or molecular subgroups.
Immune checkpoint blockade in desmoplastic melanoma - Nature Cancer
Desmoplastic melanoma, a rare form of skin cancer, is characterized by a high tumor mutational burden and is likely to benefit from treatment with immune checkpoint inhibitors. Results from a phase 2 clinical trial now suggest the efficacy of single-agent PD-1 blockade in the treatment of both resectable and unresectable desmoplastic melanoma.
Immune signature-based uncoupling of checkpoint inhibitor efficacy and toxicity
Keywords immune checkpoint inhibition personalization biomarker interferon-gamma signature neoadjuvant melanoma PD-1 CTLA-4 LAG-3 immune-related adverse events Get full text access Log in, subscribe or purchase for full access. References 1. Wolchok, J.D. ∙ Kluger, H. ∙ Callahan, M.K. ... Nivolumab plus ipilimumab in advanced melanoma N. Engl. J. Med. 2013; 369:122-133 2. Rozeman, E.A. ∙ Menzies, A.M. ∙ van Akkooi, A.C.J. ...
Upregulation of exosome secretion from tumor-associated macrophages plays a key role in the suppression of anti-tumor immunity
Highlights • Tumor-associated macrophages secrete a large amount of PD-L1+ small extracellular vesicles • Akt promotes exosome secretion in TAMs through MADD phosphorylation • TAM-derived exosomes inhibit CD8 T cell proliferation and function • Targeting macrophage RAB27A by LNPs sensitizes tumor to anti-PD-1 antibody Summary Macrophages play a pivotal role in tumor immunity. We report that reprogramming of macrophages to tumor-associated macrophages (TAMs) promotes the secretion of exosomes.
Shared and distinct biological circuits in effector, memory and exhausted CD8+ T cells revealed by temporal single-cell transcriptomics and epigenetics | Nature Immunology
Author notes Ryan Staupe Present address: Infectious Disease & Vaccines, MRL, Merck & Co. Inc., West Point, PA, USA Mohamed S. Abdel-Hakeem Present address: Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA, USA Patrick K.
Personalizing the approach to neoadjuvant therapy: a promising path to improving outcomes of resectable melanoma - Nature Reviews Clinical Oncology
Clinical trials of neoadjuvant therapy for melanoma have expanded rapidly over the past several years. Preliminary data demonstrate the prognostic value of pathological response, which might have clinical implications for refining the roles of surgery and adjuvant therapy. These clinical questions are under active investigation across many ongoing clinical trials. Refers to Reijers, I. L. M. et al.
PD-1 directed immunotherapy alters Tfh and humoral immune responses to seasonal influenza vaccine - Nature Immunology
Abstract Anti-programmed death-1 (anti-PD-1) immunotherapy reinvigorates CD8 T cell responses in patients with cancer but PD-1 is also expressed by other immune cells, including follicular helper CD4 T cells (Tfh) which are involved in germinal centre responses. Little is known, however, about the effects of anti-PD-1 immunotherapy on noncancer immune responses in humans.
HRS phosphorylation drives immunosuppressive exosome secretion and restricts CD8+ T-cell infiltration into tumors - Nature Communications
Abstract The lack of tumor infiltration by CD8+ T cells is associated with poor patient response to anti-PD-1 therapy. Understanding how tumor infiltration is regulated is key to improving treatment efficacy. Here, we report that phosphorylation of HRS, a pivotal component of the ESCRT complex involved in exosome biogenesis, restricts tumor infiltration of cytolytic CD8+ T cells.
BAMM (BRAF Autophagy and MEK inhibition in Melanoma): A phase I/II trial of dabrafenib, trametinib and hydroxychloroquine in advanced BRAFV600-mutant melanoma
Research Article Janice M. Mehnert, Tara Mitchell, Alexander C. Huang, Tomas S. Aleman, Benjamin J. Kim, Lynn M. Schuchter, Gerald P. Linette, Giorgos Karakousis, Sheryl Mitnick, Lydia Giles, Mary Carberry, Noelle Frey, Andrew Kossenkov, Roman Groisberg, Leonel F. Hernandez-Aya, George Ansstas, Ann W. Silk, Sunandana Chandra, Jeffrey A. Sosman, Phyllis A.
Building a Fraud Department and Optimizing Manual Review
Neil Hawkey -- Epoch; Ronojoy Chatterjee -- Google; Blaise Peters -- Newegg.com; Tara Mitchell -- Uber; Megan Leonetti -- Bodybuilding.com Presentation For additional insights, please see the MRC Fraud Community whitepaper "How to Create a Fraud Prevention Unit" posted here. Slides for this presentation and presenters' notes are available by signing in or becoming a member, then returning to this page.
Timing of Onset of Adverse Cutaneous Reactions Associated With Programmed Cell Death Protein 1 Inhibitor Therapy
Brief Report September 2018 JAMA Dermatol. 2018;154(9):1057-1061. doi:10.1001/jamadermatol.2018.1912 Key Points Question What is the timing of onset of cutaneous immune-related adverse reactions in patients treated with programmed cell death protein 1 inhibitors?
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