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Therapies that target the programmed death-1 (PD-1) receptor have shown unprecedented rates of durable clinical responses in patients with various cancer types. One mechanism by which cancer tissues limit the host immune response is via upregulation of PD-1 ligand (PD-L1) and its ligation to PD-1 on antigen-specific CD8(+) T cells (termed adaptive immune(More)
BACKGROUND The programmed death 1 (PD-1) receptor is a negative regulator of T-cell effector mechanisms that limits immune responses against cancer. We tested the anti-PD-1 antibody lambrolizumab (previously known as MK-3475) in patients with advanced melanoma. METHODS We administered lambrolizumab intravenously at a dose of 10 mg per kilogram of body(More)
BACKGROUND Approximately 75% of objective responses to anti-programmed death 1 (PD-1) therapy in patients with melanoma are durable, lasting for years, but delayed relapses have been noted long after initial objective tumor regression despite continuous therapy. Mechanisms of immune escape in this context are unknown. METHODS We analyzed biopsy samples(More)
Loss-of-function mutations in JAK1/2 can lead to acquired resistance to anti-programmed death protein 1 (PD-1) therapy. We reasoned that they may also be involved in primary resistance to anti-PD-1 therapy. JAK1/2-inactivating mutations were noted in tumor biopsies of 1 of 23 patients with melanoma and in 1 of 16 patients with mismatch repair-deficient(More)
Combining immunotherapy with targeted therapy blocking oncogenic BRAFV600 may result in improved treatments for advanced melanoma. In this study, we developed a BRAFV600E-driven murine model of melanoma, SM1, which is syngeneic to fully immunocompetent mice. SM1 cells exposed to the BRAF inhibitor vemurafenib (PLX4032) showed partial in vitro and in vivo(More)
In recent years, investigators have made significant progress in documenting brain structure and function as it relates to aging by using positron emission tomography, conventional magnetic resonance (MR) imaging, advanced MR techniques, and functional MR imaging. This review summarizes the latest advances in understanding physiologic maturation and aging(More)
BACKGROUND Dermatologists at the University of California, San Francisco recently reported two patients in the online Journal of the American Academy of Dermatology with purpura presumably induced by levamisole in contaminated cocaine. Levamisole-induced vasculitis and neutropenia has been reported elsewhere in the United States and Canada. Up to 70% of(More)
Immune system activation can be elicited in viral infections, active immunization, or cancer immunotherapy, leading to the final common phenotype of increased glycolytic use by immune cells and subsequent detection by 18F-FDG PET. Because 18F-FDG is also used in baseline staging PET/CT scans and in tumor response assessment, physicians are faced with a(More)
Targeting immune inhibitory receptors has brought excitement, innovation and hope to cancer patients. Our recent work revealed the immunological effects of blocking the CTLA4 and PD-1 immune checkpoints on T cell receptor usage among peripheral blood cells, and further uncovers how the expansion of the T cell repertoire matches the immunotoxicity profile of(More)