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Melanoma pd-1

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https://www.readbyqxmd.com/read/28214182/opportunistic-autoimmunity-secondary-to-cancer-immunotherapy-oasi-an-emerging-challenge
#1
M Kostine, L Chiche, E Lazaro, P Halfon, C Charpin, D Arniaud, F Retornaz, P Blanco, N Jourde-Chiche, C Richez, C Stavris
With "checkpoint inhibitors" targeting PD1/PD-1-ligands or CTLA-4/CD28 pathways, immunotherapy has profoundly modified therapeutic strategies in oncology. First approved in refractory metastatic neoplasms (melanoma and lung adenocarcinoma), it is now being tested broadly in other cancers and/or as adjuvant treatment. For a significant proportion of patients, immunotherapy is responsible for "immunological" events, identified as Immune-Related Adverse Events (irAEs). Owing to the increasing number of prescriptions, identification and management of specific immunological side effects is crucial and requires close collaboration between oncologists and internists and/or other organ specialists...
February 14, 2017: La Revue de Médecine Interne
https://www.readbyqxmd.com/read/28213726/pd-1-and-pd-l1-antibodies-in-cancer-current-status-and-future-directions
#2
REVIEW
Arjun Vasant Balar, Jeffrey S Weber
Immunotherapy has moved to the center stage of cancer treatment with the recent success of trials in solid tumors with PD-1/PD-L1 axis blockade. Programmed death-1 or PD-1 is a checkpoint molecule on T cells that plays a vital role in limiting adaptive immune responses and preventing autoimmune and auto-inflammatory reactivity in the normal host. In cancer patients, PD-1 expression is very high on T cells in the tumor microenvironment, and PD-L1, its primary ligand, is variably expressed on tumor cells and antigen-presenting cells within tumors, providing a potent inhibitory influence within the tumor microenvironment...
February 17, 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/28211077/severe-bullous-pemphigoid-associated-with-pembrolizumab-therapy-for-metastatic-melanoma-with-complete-regression
#3
O Rofe, G Bar-Sela, Z Keidar, T Sezin, C D Sadik, R Bergman
Bullous pemphigoid (BP) is considered to be a humorally mediated autoimmune disease, but autoreactive T-cells and T-regulatory cells (Tregs) have also been implicated in this disease. Tregs and the programmed death-1 (PD-1) : programmed death ligand (PD-L) pathway are both critical in terminating immune response, and elimination of either can result in breakdown of tolerance and development of autoimmunity. We report a patient with metastatic malignant melanoma (MM), who underwent pembrolizumab (anti-PD-1) therapy following unsuccessful treatment with ipilimumab [anti-cytotoxic T-lymphocyte-associated protein (CTLA)-4]...
February 16, 2017: Clinical and Experimental Dermatology
https://www.readbyqxmd.com/read/28210865/the-impact-of-melanoma-genetics-on-treatment-response-and-resistance-in-clinical-and-experimental-studies
#4
M Kunz, M Hölzel
Recent attempts to characterize the melanoma mutational landscape using high-throughput sequencing technologies have identified new genes and pathways involved in the molecular pathogenesis of melanoma. Apart from mutated BRAF, NRAS, and KIT, a series of new recurrently mutated candidate genes with impact on signaling pathways have been identified such as NF1, PTEN, IDH1, RAC1, ARID2, and TP53. Under targeted treatment using BRAF and MEK1/2 inhibitors either alone or in combination, a majority of patients experience recurrences, which are due to different genetic mechanisms such as gene amplifications of BRAF or NRAS, MEK1/2 and PI3K mutations...
February 16, 2017: Cancer Metastasis Reviews
https://www.readbyqxmd.com/read/28204866/vedolizumab-treatment-for-immune-checkpoint-inhibitor-induced-enterocolitis
#5
Viktoria Bergqvist, Erik Hertervig, Peter Gedeon, Marija Kopljar, Håkan Griph, Sara Kinhult, Ana Carneiro, Jan Marsal
Immune checkpoint inhibitors (ICPI), such as ipilimumab [anti-cytotoxic T-lymphocyte antigen-4 (CTLA-4) antibody] and nivolumab or pembrolizumab [anti-programmed cell death protein-1 (PD-1) antibodies], improve survival in several cancer types. Since inhibition of CTLA-4 or PD-1 leads to non-selective activation of the immune system, immune-related adverse events (irAEs) are frequent. Enterocolitis is a common irAE, currently managed with corticosteroids and, if necessary, anti-tumor necrosis factor-α therapy...
February 15, 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/28202614/virus-specific-cd8-t-cells-infiltrate-melanoma-lesions-and-retain-function-independently-of-pd-1-expression
#6
Dan A Erkes, Corinne J Smith, Nicole A Wilski, Sofia Caldeira-Dantas, Toktam Mohgbeli, Christopher M Snyder
It is well known that CD8(+) tumor-infiltrating lymphocytes (TILs) are correlated with positive prognoses in cancer patients and are used to determine the efficacy of immune therapies. Although it is generally assumed that CD8(+) TILs will be tumor-associated Ag (TAA) specific, it is unknown whether CD8(+) T cells with specificity for common pathogens also infiltrate tumors. If so, the presence of these T cells could alter the interpretation of prognostic and diagnostic TIL assays. We compared TAA-specific and virus-specific CD8(+) T cells in the same tumors using murine CMV, a herpesvirus that causes a persistent/latent infection, and vaccinia virus, a poxvirus that is cleared by the host...
February 15, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28202513/myeloid-cells-that-impair-immunotherapy-are-restored-in-melanomas-which-acquire-resistance-to-braf-inhibitors
#7
Shannon M Steinberg, Tamer Shabaneh, Peisheng Zhang, Viktor Martyanov, Zhenghui Li, Brian Malik, Tammara Wood, Andrea Boni, Aleksey Molodtsov, Christina V Angeles, Tyler J Curiel, Michael Whitfield, Mary Jo Turk
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 the plastic nature of cancers. While there has been significant focus on the cancer cell-intrinsic properties of BRAFi resistance, the impact of BRAFi resistance on host immunity has not been explored. Here we provide preclinical evidence that resistance to BRAFi in an autochthonous mouse model of melanoma is associated with restoration of myeloid-derived suppressor cells (MDSC) in the tumor microenvironment initially reduced by BRAFi treatment...
February 15, 2017: Cancer Research
https://www.readbyqxmd.com/read/28197351/a-case-of-malignant-melanoma-of-the-uterine-cervix-with-disseminated-metastases-throughout-the-vaginal-wall
#8
Tomoko Noguchi, Nami Ota, Yasushi Mabuchi, Shigetaka Yagi, Sawako Minami, Hisako Okuhira, Yuki Yamamoto, Yasushi Nakamura, Kazuhiko Ino
Malignant melanoma (MM) in the female genital tract accounts for less than 2% of all melanomas, and the vast majority associated occur in the vulva and vagina. Primary MM of the uterine cervix is extremely rare and its prognosis is very poor. We report a case of primary MM of the cervix with dissemination throughout the vaginal wall. A 66-year-old woman presented with postmenopausal bleeding. Gynecologic examination demonstrated a 2 cm polypoid blackish-pigmented tumor on the cervix with multiple small blackish-pigmented lesions throughout the vaginal wall...
2017: Case Reports in Obstetrics and Gynecology
https://www.readbyqxmd.com/read/28194491/-merkel-cell-carcinoma-cutaneous-manifestation-of-a-highly-malignant-pre-pro-b%C3%A2-cell-neoplasia-novel-concept-about-the-cellular-origin-of-merkel-cell-carcinoma
#9
REVIEW
C M Sauer, E Chteinberg, D Rennspiess, A K Kurz, A Zur Hausen
Merkel cell carcinoma (MCC) is a relatively rare but highly malignant non-melanoma skin cancer of the elderly and immunosuppressed patients. The discovery of the Merkel cell polyomavirus (MCPyV) in 2008 significantly impacted the understanding of the etiopathogenesis of MCC. MCPyV is clonally integrated into the MCC genome and approximately 80% of MCC are MCPyV-positive. Recent results of clinical trials using blockade of the PD-1 immune modulatory pathway are promising for the future treatment of MCC. Despite this major progress of the past few years, the cellular origin of MCC still remains obscure...
February 13, 2017: Der Hautarzt; Zeitschrift Für Dermatologie, Venerologie, und Verwandte Gebiete
https://www.readbyqxmd.com/read/28193624/transcriptional-mechanisms-of-resistance-to-anti-pd-1-therapy
#10
Maria Libera Ascierto, Alvin Makohon-Moore, Evan J Lipson, Janis M Taube, Tracee L McMiller, Alan E Berger, Jinshui Fan, Genevieve Kaunitz, Tricia Cottrell, Zachary Kohutek, Alexander Favorov, Vladimir Makarov, Nadeem Riaz, Timothy A Chan, Leslie Cope, Ralph H Hruban, Drew M Pardoll, Barry S Taylor, David B Solit, Christine A Iacobuzio-Donahue, Suzanne L Topalian
PURPOSE: To explore factors associated with response and resistance to anti-PD-1 therapy, we analyzed multiple disease sites at autopsy in a patient with widely metastatic melanoma who had a heterogeneous response. MATERIALS AND METHODS: Twenty-six melanoma specimens (four pre-mortem, 22 post-mortem) were subjected to whole-exome sequencing. Candidate immunologic markers and gene expression were assessed in ten cutaneous metastases showing response or progression during therapy...
February 13, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28190531/cutaneous-adverse-effects-of-the-immune-checkpoint-inhibitors
#11
REVIEW
Lindsey K Collins, M Shane Chapman, Joi B Carter, Faramarz H Samie
The immune checkpoint targeted agents, anti-cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) and anti-programed cell death 1 (PD-1) or anti-programmed death ligand 1 (PD-L1) inhibitors are frequently associated with cutaneous side effects that are often dose limiting and can lead to discontinuation of therapy. Ipilimumab, a CTLA-4 inhibitor, is most commonly associated with a morbilliform eruption on the trunk and extremities and pruritus. More severe cutaneous toxicities reported include toxic epidermal necrolysis and severe drug rash with eosinophila and systemic symptoms...
December 14, 2016: Current Problems in Cancer
https://www.readbyqxmd.com/read/28188628/histopathological-aspects-of-cutaneous-erythematous-papular-eruptions-induced-by-immune-checkpoint-inhibitors-for-the-treatment-of-metastatic-melanoma
#12
Raul E Perret, Nicolas Josselin, Anne-Chantal Knol, Amir Khammari, Julie Cassecuel, Lucie Peuvrel, Brigitte Dreno
BACKGROUND: Immune checkpoint blockade therapy (ICBT) for the treatment of melanoma has led to an important improvement of overall survival in advanced stage patients. However, secondary cutaneous maculopapular eruptions (CMPEs) are frequent and remain poorly characterized. METHODS: We performed a retrospective analysis of melanoma patients from our institution who developed CMPEs during ICBT. Clinical information was retrieved, and histopathological and immunohistochemical characterization was performed by two pathologists...
February 10, 2017: International Journal of Dermatology
https://www.readbyqxmd.com/read/28184224/cbl-b-deficiency-mediates-resistance-to-programmed-death-ligand-1-programmed-death-1-regulation
#13
Mai Fujiwara, Emily J Anstadt, Robert B Clark
Casitas B-lineage lymphoma-b (Cbl-b) is an E3 ubiquitin ligase that negatively regulates T cell activation. Cbl-b(-/-) T cells are hyper-reactive and co-stimulation independent, and Cbl-b(-/-) mice demonstrate robust T cell and NK cell-mediated antitumor immunity. As a result of these murine studies, Cbl-b is considered a potential target for therapeutic manipulation in human cancer immunotherapy. The PD-L1/PD-1 pathway of immune regulation is presently an important therapeutic focus in tumor immunotherapy, and although Cbl-b(-/-) mice have been shown to be resistant to several immuno-regulatory mechanisms, the sensitivity of Cbl-b(-/-) mice to PD-L1-mediated suppression has not been reported...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28181070/combining-forces-the-promise-and-peril-of-synergistic-immune-checkpoint-blockade-and-targeted-therapy-in-metastatic-melanoma
#14
David J Hermel, Patrick Ott
Both immune checkpoint inhibitors and molecularly targeted agents have dramatically improved clinical outcomes for patients with metastatic melanoma. These two therapeutic approaches harness distinct mechanistic pathways-on the one hand, monoclonal antibodies against the immune checkpoints CTLA-4 and PD-1/PD-L1 stimulate the T cell mediated host immune response, while targeted inhibitors of the proto-oncogenes BRAF and MEK disrupt constitutive kinase activity responsible for tumor growth. The prospect of combining these two treatment modalities has been proposed as a potential way to increase overall response rate, extend durability of the anti-tumor response, and circumvent the immune-mediated resistance to targeted therapy...
February 8, 2017: Cancer Metastasis Reviews
https://www.readbyqxmd.com/read/28174141/checkpoint-inhibition-for-advanced-mucosal-melanoma
#15
Julia Thierauf, Johannes A Veit, Jochen Hess, Nicolai Treiber, Catharina Lisson, Stephanie E Weissinger, Martin Bommer, Thomas K Hoffmann
BACKGROUND: Whereas anti-PD-1 therapy has demonstrated a significant and durable response against advanced cutaneous melanoma, conventional chemotherapies have shown only minor benefit against advanced mucosal melanoma. OBJECTIVES: To investigate the efficacy of anti-PD-1 therapy in a small cohort of patients with mucosal melanoma of the head and neck. MATERIAL & METHODS: We analysed five patients with mucosal melanoma of the head and neck who received nivolumab or pembrolizumab, at an advanced stage...
February 3, 2017: European Journal of Dermatology: EJD
https://www.readbyqxmd.com/read/28171845/a-first-reported-case-of-metastatic-anorectal-amelanotic-melanoma-with-a-marked-response-to-anti-pd-1-antibody-nivolumab-a-case-report
#16
Katsuji Tokuhara, Kazuyoshi Nakatani, Hirotsugu Tanimura, Kazuhiko Yoshioka, Takahiro Kiyohara, Masanori Kon
INTRODUCTION: Anorectal amelanotic melanoma (AAMM) is a rare disease with poor prognosis. A standard treatment strategy for AAMM has not been established. PRESENTATION OF CASE: We report a case of successful treatment of AAMM with nivolumab. A 67-year-old man was referred for colonoscopy which revealed type I tumor in the rectum. AAMM was diagnosed with immunostaining histopathological biopsy findings. Enhanced computed tomography (ECT) revealed the rectal tumor without distant organ metastasis...
January 23, 2017: International Journal of Surgery Case Reports
https://www.readbyqxmd.com/read/28167454/peripheral-cd8-effector-memory-type-1-t-cells-correlate-with-outcome-in-ipilimumab-treated-stage-iv-melanoma-patients
#17
Kilian Wistuba-Hamprecht, Alexander Martens, Florian Heubach, Emanuela Romano, Marnix Geukes Foppen, Jianda Yuan, Michael Postow, Phillip Wong, Domenico Mallardo, Bastian Schilling, Anna Maria Di Giacomo, Amir Khammari, Brigitte Dreno, Michele Maio, Dirk Schadendorf, Paolo A Ascierto, Jedd D Wolchok, Christian U Blank, Claus Garbe, Graham Pawelec, Benjamin Weide
The role of the assessment of peripheral T-cell phenotypes in predicting overall survival (OS) after ipilimumab treatment is unclear. Here, we analysed mononuclear cells in the blood before and at different time points during treatment with ipilimumab in 137 late-stage melanoma patients. The proportions of baseline naïve and memory T-cells were measured by flow cytometry and correlated with OS, with an emphasis on PD-1 expression. High frequencies (>13%) of CD8 effector-memory type 1 (EM1) T-cells at baseline correlated with longer OS (p = 0...
February 3, 2017: European Journal of Cancer
https://www.readbyqxmd.com/read/28166182/vogt-koyanagi-harada-like-syndrome-complicating-pembrolizumab-treatment-for-metastatic-melanoma
#18
Marion Bricout, Adeline Petre, Mona Amini-Adle, Widad Bezza, Pascal Seve, Laurent Kodjikian, Stéphane Dalle, Luc Thomas
Vogt-Koyanagi-Harada (VKH) syndrome is a rare condition implicating systemic immune reaction against melanocytes. The pathophysiology is unclear. A genetic predisposition has been suggested as HLA-DR4/DRB1*04 is more common among VKH patients. Drug induced VKH syndrome has been reported in advanced melanoma patients receiving immunotherapy, including ipilimumab and adoptive cell transfer of Tumor-Infiltrating Lymphocyte associated with IL-2. To date, no case of anti PD-1 -induced VKH syndrome has been described...
February 2017: Journal of Immunotherapy
https://www.readbyqxmd.com/read/28161431/dosimetric-and-radiobiologic-comparison-of-103-pd-coms-plaque-brachytherapy-and-gamma-knife-radiosurgery-for-choroidal-melanoma
#19
Daniel Gorovets, Nolan L Gagne, Christopher S Melhus
PURPOSE: Plaque brachytherapy (BT) and Gamma Knife radiosurgery (GKRS) are highly conformal treatment options for choroidal melanoma. This study objectively compares physical dose and biologically effective dose (BED) distributions for these two modalities. METHODS AND MATERIALS: Tumor and organ-at-risk (OAR) dose distributions from a CT-defined reference right eye were compared between (103)Pd COMS (Collaborative Ocular Melanoma Study Group) plaques delivering 70 Gy (plaque heterogeneity corrected) over 120 h to the tumor apex and GKRS plans delivering 22 Gy to the 40% isodose line for a representative sample of clinically relevant choroidal melanoma locations and sizes...
February 1, 2017: Brachytherapy
https://www.readbyqxmd.com/read/28158487/short-term-ctla-4-blockade-directly-followed-by-pd-1-blockade-in-advanced-melanoma-patients-a-single-center-experience
#20
A Meerveld-Eggink, E A Rozeman, F Lalezari, J V van Thienen, J B A G Haanen, C U Blank
No abstract text is available yet for this article.
February 2, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
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