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Melanoma pd-1

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https://www.readbyqxmd.com/read/28105370/interstitial-nephritis-in-melanoma-patients-secondary-to-pd-1-checkpoint-inhibitor
#1
Julia Escandon, Stephanie Peacock, Asaad Trabolsi, David B Thomas, Ayman Layka, Jose Lutzky
BACKGROUND: Immune checkpoint inhibitors have become the first line therapy in melanoma treatment and their use is extending to other malignancies. However, we are still learning about immune side effects produced by these drugs and their severity especially in patients with history of inflammatory diseases. CASE PRESENTATION: We present two cases of metastatic melanoma treated with nivolumab and pembrolizumab (anti PD-1). Both patients developed acute interstitial nephritis during immune checkpoint therapy...
2017: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/28099369/the-cessation-of-anti-pd-1-antibodies-of-complete-responders-in-metastatic-melanoma
#2
Rahul Ladwa, Victoria Atkinson
The optimal duration of PD-1 antibodies for metastatic melanoma is unknown. In previous trials, there has been the potential to cease therapy if the patient achieves a complete response (CR). We aimed to assess the outcomes of patients who had ceased anti-PD-1 antibodies in this setting. A retrospective review was carried out of CR to PD-1-based therapy across two institutions. Patients were from the Pembrolizumab Named Patient Program (PEM NPP), Nivolumab monotherapy (NIVO), and reimbursed Pembrolizumab (r PEM)...
January 17, 2017: Melanoma Research
https://www.readbyqxmd.com/read/28097229/anti-sirp%C3%AE-antibodies-as-a-potential-new-tool-for-cancer-immunotherapy
#3
Tadahiko Yanagita, Yoji Murata, Daisuke Tanaka, Sei-Ichiro Motegi, Eri Arai, Edwin Widyanto Daniwijaya, Daisuke Hazama, Ken Washio, Yasuyuki Saito, Takenori Kotani, Hiroshi Ohnishi, Per-Arne Oldenborg, Noel Verjan Garcia, Masayuki Miyasaka, Osamu Ishikawa, Yae Kanai, Takahide Komori, Takashi Matozaki
Tumor cells are thought to evade immune surveillance through interaction with immune cells. Much recent attention has focused on the modification of immune responses as a basis for new cancer treatments. SIRPα is an Ig superfamily protein that inhibits phagocytosis in macrophages upon interaction with its ligand CD47 expressed on the surface of target cells. Here, we show that SIRPα is highly expressed in human renal cell carcinoma and melanoma. Furthermore, an anti-SIRPα Ab that blocks the interaction with CD47 markedly suppressed tumor formation by renal cell carcinoma or melanoma cells in immunocompetent syngeneic mice...
January 12, 2017: JCI Insight
https://www.readbyqxmd.com/read/28096186/translation-reprogramming-is-an-evolutionarily-conserved-driver-of-phenotypic-plasticity-and-therapeutic-resistance-in-melanoma
#4
Paola Falletta, Luis Sanchez-Del-Campo, Jagat Chauhan, Maike Effern, Amy Kenyon, Christopher J Kershaw, Robert Siddaway, Richard Lisle, Rasmus Freter, Matthew J Daniels, Xin Lu, Thomas Tüting, Mark Middleton, Francesca M Buffa, Anne E Willis, Graham Pavitt, Ze'ev A Ronai, Tatjana Sauka-Spengler, Michael Hölzel, Colin R Goding
The intratumor microenvironment generates phenotypically distinct but interconvertible malignant cell subpopulations that fuel metastatic spread and therapeutic resistance. Whether different microenvironmental cues impose invasive or therapy-resistant phenotypes via a common mechanism is unknown. In melanoma, low expression of the lineage survival oncogene microphthalmia-associated transcription factor (MITF) correlates with invasion, senescence, and drug resistance. However, how MITF is suppressed in vivo and how MITF-low cells in tumors escape senescence are poorly understood...
January 17, 2017: Genes & Development
https://www.readbyqxmd.com/read/28076863/adverse-renal-effects-of-immune-checkpoint-inhibitors-a-narrative-review
#5
Rimda Wanchoo, Sabine Karam, Nupur N Uppal, Valerie S Barta, Gilbert Deray, Craig Devoe, Vincent Launay-Vacher, Kenar D Jhaveri
BACKGROUND: Cancer immunotherapy, such as anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and anti-programmed death 1 (PD-1), has revolutionized the treatment of malignancies by engaging the patient's own immune system against the tumor rather than targeting the cancer directly. These therapies have demonstrated a significant benefit in the treatment of melanomas and other cancers. SUMMARY: In order to provide an extensive overview of the renal toxicities induced by these agents, a Medline search was conducted of published literature related to ipilimumab-, pembrolizumab-, and nivolumab-induced kidney toxicity...
January 12, 2017: American Journal of Nephrology
https://www.readbyqxmd.com/read/28072717/clinics-prognosis-and-new-therapeutic-options-in-patients-with-mucosal-melanoma-a-retrospective-analysis-of-75-patients
#6
Tim Schaefer, Imke Satzger, Ralf Gutzmer
Mucosal melanomas represent a rare entity with different risk factors and molecular features compared to cutaneous melanomas. They arise most commonly from mucosal surfaces in the head/neck region, the female genital tract (FGT) and the anorectal region. The aim of this study was to evaluate clinics, prognosis, and treatment options of patients with mucosal melanoma, in particular with regard to different primary sites.We retrospectively analyzed 75 patients with mucosal melanomas diagnosed in the years 1993 to 2015 in our department...
January 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/28062513/metastatic-melanoma-patient-had-complete-response-with-clonal-expansion-after-whole-brain-radiation-and-pd-1-blockade
#7
Cara L Haymaker, DaeWon Kim, Marc Uemura, Luis M Vence, Ann Phillip, Natalie McQuail, Paul D Brown, Irina Fernandez, Courtney W Hudgens, Caitlin Creasy, Wen-Jen Hwu, Padmanee Sharma, Michael T Tetzlaff, James P Allison, Patrick Hwu, Chantale Bernatchez, Adi Diab
We report here on a patient with metastatic melanoma who had extensive brain metastases. After being treated with the sequential combination of whole brain radiation therapy (WBRT) followed by the PD-1 inhibitory antibody, pembrolizumab, the patient had a durable complete response. Retrospective laboratory studies of T cells revealed that, after treatment with anti-PD-1 commenced, effector CD8(+) T cells in the blood expanded and the ratio of CD8(+):Treg T cells increased. A CD8(+) T-cell clone present in the initial brain metastases was expanded in the blood after anti-PD-1 treatment, which suggested an antitumor role for this clone...
January 6, 2017: Cancer Immunology Research
https://www.readbyqxmd.com/read/28058578/pd-l1-expression-and-tumor-infiltrating-pd-1-%C3%A2-lymphocytes-associated-with-outcome-in-her2-%C3%A2-breast-cancer-patients
#8
Julia Y S Tsang, Wai-Ling Au, Kwan-Yin Lo, Yun-Bi Ni, Thazin Hlaing, Jintao Hu, Siu-Ki Chan, Kui-Fat Chan, Sai-Yin Cheung, Gary M Tse
PURPOSE: Clinical trials showing programmed death (PD)-1-PD-ligand 1 (L1) axis as a promising therapeutic target in melanoma and non-small cell lung cancers have made the pathway a focus of recent attention. However, the data regarding PD-L1/PD-1 in breast cancer are inconsistent. Given the heterogeneity of breast cancers, the clinical relevance of PD-L1 and PD-1 tumor infiltrating lymphocytes (TIL) may vary according to subtypes of breast cancer. We aim to investigate PD-L1 expression in a large cohort of breast cancers and analyze its clinico-pathological as well as outcome relationship according to molecular subtypes...
January 5, 2017: Breast Cancer Research and Treatment
https://www.readbyqxmd.com/read/28057179/biomarqueurs-pr%C3%A3-dictifs-de-r%C3%A3-ponse-aux-traitements-bloquant-les-voies-de-costimulation-inhibitrices
#9
Franck Pagès, Clémence Granier, Amos Kirilovsky, Carine Elsissy, Eric Tartour
Immunotherapies targeting co-inhibitory receptors recently open a new promising approach of cancer treatment. Indeed, an objective clinical response was observed after treatment by anti-CTLA-4 and anti-PD-1 in many indications but the treatment still failed in 70 to 80 % of cases treated. Given the adverse effects and the high cost of these therapies, there is a need for the development of biomarkers. This review focus on potential predictive biomarkers. In peripheral blood, high level of Il-2 soluble receptor at baseline and absence of ICOS+ CD4-T lymphocytes induction may be associated with the absence of clinical response for melanoma patients treated by ipilimumab (anti-CTLA-4)...
November 2016: Bulletin du Cancer
https://www.readbyqxmd.com/read/28057176/immunoth%C3%A3-rapie-et-m%C3%A3-lanome-l%C3%A2-exemple-des-anticorps-immunomodulateurs
#10
Cécile Pagès, Barouyr Baroudjian, Celeste Lebbé
Recently, metastatic melanoma has known real therapeutic improvement. Since 2011, 8 drugs have been approved for advanced melanoma such as immunotherapy checkpoint inhibitors. Chemotherapy is no longer used in the first setting of metastatic melanoma treatment. In 2010, the advent of ipilimumab, an anti CTLA 4 inhibitor, changed the scenario and in the following years, many studies confirmed the efficacy of nivolumab and pembrolizumab, two anti PD 1 inhibitors, as a first line treatment. Furthermore, the combination of first-line nivolumab plus ipilimumab might lead to improved outcomes compared with first-line ipilimumab alone in patients with advanced melanoma...
November 2016: Bulletin du Cancer
https://www.readbyqxmd.com/read/28055269/targeting-pd-1-pathway-a-new-hope-for-gastrointestinal-cancers
#11
Burak Bilgin, Mehmet An Sendur, Muhammed Bülent Akıncı, Didem Şener Dede, Bülent Yalçın
BACKGROUND: VEGF, HER2 and EGFR targeted agents are currently used in gastric, esophageal and colorectal cancers. However, treatment outcomes are still poor in most of the Gastrointestinal (GI) cancers. Immune checkpoints are one of the most promising immunotherapy approaches. In this review article, we aimed to discuss the efficacy and safety of anti-PD-1/PD-L1 therapies in GI cancers, including gastric, esophageal and colorectal cancer in the era of published or reported recent studies...
January 5, 2017: Current Medical Research and Opinion
https://www.readbyqxmd.com/read/28054320/pembrolizumab-for-advanced-melanoma-experience-from-the-spanish-expanded-access-program
#12
M González-Cao, A Arance, J M Piulats, I Marquez-Rodas, J L Manzano, A Berrocal, G Crespo, D Rodriguez, E Perez-Ruiz, M Berciano, A Soria, A G Castano, E Espinosa, C Montagut, L Alonso, T Puertolas, C Aguado, M A Royo, R Blanco, J F Rodríguez, E Muñoz, P Mut, F Barron, S Martin-Algarra
BACKGROUND: The programmed death (PD-1) inhibitor pembrolizumab has been recently approved for the treatment of advanced melanoma. We evaluated the clinical activity of pembrolizumab in melanoma patients treated under the Spanish Expanded Access Program. METHODS: Advanced melanoma patients who failed to previous treatment lines were treated with pembrolizumab 2 mg/kg every three weeks. Patients with brain metastases were not excluded if they were asymptomatic. Data were retrospectively collected from 21 centers in the Spanish Melanoma Group...
January 4, 2017: Clinical & Translational Oncology
https://www.readbyqxmd.com/read/28046271/su-f-t-659-nanoparticle-aided-eye-plaque-radiotherapy
#13
J Chin, W Ngwa
PURPOSE: Eye plaque brachytherapy is one of the approaches for radiotherapy treatment for ocular cancers: retinoblastoma and choroidal melanoma. This study, investigates the potential benefits of using gold nanoparticles to enhance therapeutic efficacy during eye plaque brachytherapy. METHODS: The EYE PHYSICS Inc. Plaque Simulator program distributed by IsoAid, LLC, Port Richey, Florida was used. It is based on the superposition of dose contributions from individual seeds following the TG-43 formalism...
June 2016: Medical Physics
https://www.readbyqxmd.com/read/28045203/pd-l1-expression-and-survival-among-melanoma-patients-treated-with-standard-immunotherapy-or-chemotherapy
#14
T Steiniche, A Vestergaard Danielsen, Z Wang, Y Feng, P Switten Nielsen, L Bastholt, H Schmidt, I M Svane, M Dolled-Filhart, K Emancipator, R Weiner, M Busch-Sørensen, W Zhou
The association between programmed death ligand 1 (PD-L1) expression and survival among melanoma patients treated with chemotherapy is unclear.(1-5) We retrospectively characterized PD-L1 levels in patients with melanoma treated at Aarhus University Hospital in Denmark (2001-2012) using a prototype immunohistochemistry assay (QualTek Molecular Laboratories, Goleta, California, USA) and investigated the association between PD-L1 and overall survival (OS) in patients who received chemotherapy or immunotherapy (interleukin-2, interferon, ipilimumab)...
January 3, 2017: Journal of the European Academy of Dermatology and Venereology: JEADV
https://www.readbyqxmd.com/read/28039358/stromal-senescence-by-prolonged-cdk4-6-inhibition-potentiates-tumor-growth
#15
Xiangnan Guan, Kyle M LaPak, Rebecca C Hennessey, Christina Y Yu, Reena Shakya, Jianying Zhang, Christin E Burd
: Senescent cells within the tumor microenvironment (TME) adopt a pro-inflammatory, senescence-associated secretory phenotype (SASP) that promotes cancer initiation, progression and therapeutic resistance. Here, exposure to Palbociclib (PD-0332991), a CDK4/6 inhibitor, induces senescence and a robust SASP in normal fibroblasts. Senescence caused by prolonged CDK4/6 inhibition is DNA damage-independent and associated with Mdm2 downregulation, whereas the SASP elicited by these cells is largely reliant upon NF-kappaB activation...
December 30, 2016: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/28030901/radiotherapy-and-immune-checkpoint-blockades-a-snapshot-in-2016
#16
REVIEW
Taeryool Koo, In Ah Kim
Immune checkpoint blockades including monoclonal antibodies (mAbs) of cytotoxic T-lymphocyte antigen-4 (CTLA-4), programmed death-1 (PD-1), and programmed death-ligand 1 (PD-L1) have been emerged as a promising anticancer therapy. Several immune checkpoint blockades have been approved by US Food and Drug Administration (FDA), and have shown notable success in clinical trials for patients with advanced melanoma and non-small cell lung cancer. Radiotherapy is a promising combination partner of immune checkpoint blockades due to its potent pro-immune effect...
December 2016: Radiation Oncology Journal
https://www.readbyqxmd.com/read/28028828/thyroid-abnormalities-following-the-use-of-ctla-4-and-pd-1-inhibitors-in-the-treatment-of-melanoma
#17
D L Morganstein, Z Lai, L Spain, S Diem, D Levine, C Mace, M Gore, J Larkin
CONTEXT: Checkpoint inhibitors are emerging as important cancer therapies, but are associated with a high rate of immune side effects, including endocrinopathy. OBJECTIVE: To determine the burden of thyroid dysfunction in patients with melanoma treated with immune checkpoint inhibitors and describe the clinical course. DESIGN AND PATIENTS: Consecutive patients with melanoma treated with either Ipilimumab, Nivolumab, Pembrolizumab or the combination of Ipilimumab and Nivolumab were identified...
December 27, 2016: Clinical Endocrinology
https://www.readbyqxmd.com/read/28026870/vulvar-and-vaginal-melanoma-a-unique-subclass-of-mucosal-melanoma-based-on-a-comprehensive-molecular-analysis-of-51-cases-compared-with-2253-cases-of-nongynecologic-melanoma
#18
June Y Hou, Caitlin Baptiste, Radhika Bangalore Hombalegowda, Ana I Tergas, Rebecca Feldman, Nathaniel L Jones, Sudeshna Chatterjee-Paer, Ama Bus-Kwolfski, Jason D Wright, William M Burke
BACKGROUND: Optimal treatments for vulvar and vaginal melanomas (VVMs) have not been identified. Herein, the authors compare molecular profiles between VVM and nongynecologic melanoma (NGM) subtypes with the objective of identifying novel, targetable biomarkers. METHODS: In total, 2304 samples of malignant melanoma that were submitted to Caris Life Sciences between 2009 and 2015 were reviewed. In situ hybridization and immunohistochemistry were used to assess copy numbers and protein expression of selected genes...
December 27, 2016: Cancer
https://www.readbyqxmd.com/read/28003187/angiopoietin-2-as-a-biomarker-and-target-for-immune-checkpoint-therapy
#19
Xinqi Wu, Anita Giobbie-Hurder, Xiaoyun Liao, Courtney Connelly, Erin M Connolly, Jingjing Li, Michael P Manos, Donald Lawrence, David McDermott, Mariano Severgnini, Jun Zhou, Evisa Gjini, Ana Lako, Mikel Lipschitz, Christine J Pak, Sara Abdelrahman, Scott Rodig, F Stephen Hodi
Immune checkpoint therapies targeting CTLA-4 and PD-1 have proven effective in cancer treatment. However, the identification of biomarkers for predicting clinical outcomes and mechanisms to overcome resistance remain as critical needs. Angiogenesis is increasingly appreciated as an immune modulator with potential for combinatorial use with checkpoint blockade. Angiopoietin-2 (ANGPT2) is an immune target in patients and is involved in resistance to anti-VEGF treatment with the monoclonal antibody bevacizumab...
January 2017: Cancer Immunology Research
https://www.readbyqxmd.com/read/28000302/pd-1-inhibitor-gastroenterocolitis-case-series-and-appraisal-of-immunomodulatory-gastroenterocolitis
#20
Raul S Gonzalez, Safia N Salaria, Caitlin D Bohannon, Aaron R Huber, Michael M Feely, Chanjuan Shi
AIMS: PD-1 inhibitors facilitate immune response against certain tumour types, including melanoma. These drugs have led to prolonged survival but can also result in autoimmune-type side effects, including gastrointestinal inflammation. The histopathological effects of this medication class have not been well studied. METHODS AND RESULTS: We identified 37 gastrointestinal tract biopsies from 20 patients taking a PD-1 or PD-L1 inhibitor and evaluated clinicopathological findings...
November 7, 2016: Histopathology
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