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Melanoma pd-1

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https://www.readbyqxmd.com/read/28730266/-malignant-melanoma-current-status
#1
REVIEW
J K Winkler, K Buder-Bakhaya, A Dimitrakopoulou-Strauss, A Enk, J C Hassel
CLINICAL ISSUE: The incidence of malignant melanoma is continuously increasing. The prognosis of metastatic disease is still limited. STANDARD TREATMENT: Until a few years ago palliative chemotherapy with a limited response rate was the standard treatment for metastatic melanoma. TREATMENT INNOVATIONS: Immunotherapy and targeted therapy provide new treatment options. Immune checkpoint inhibitors have significantly improved the prognosis. DIAGNOSTIC WORK-UP: Regional lymph node sonography, computed tomography (CT) of the neck, chest and abdomen and brain magnetic resonance imaging (MRI) are routinely used...
July 20, 2017: Der Radiologe
https://www.readbyqxmd.com/read/28730140/current-advances-in-checkpoint-inhibitors-lessons-from-non-central-nervous-system-cancers-and-potential-for-glioblastoma
#2
REVIEW
Natasha Lakin, Robert Rulach, Stefan Nowicki, Kathreena M Kurian
The adaptive immune system depends on the sequence of antigen presentation, activation, and then inhibition to mount a proportionate response to a threat. Tumors evade the immune response partly by suppressing T-cell activity using immune checkpoints. The use of cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), programmed cell death 1 (PD-1), and programmed cell death ligand 1 (PD-L1) antibodies counteract this suppression, thereby enhancing the antitumor activity of the immune system. This approach has proven efficacy in melanoma, renal cancer, and lung cancer...
2017: Frontiers in Oncology
https://www.readbyqxmd.com/read/28725431/angiosarcoma-treated-successfully-with-anti-pd-1-therapy-a-case-report
#3
Simran Sindhu, Lana H Gimber, Lee Cranmer, Ali McBride, Andrew S Kraft
BACKGROUND: Angiosarcomas are tumors of malignant endothelial origin that have a poor prognosis with a five-year survival of less than 40%. These tumors can be found in all age groups, but are more common in older patients; with the cutaneous form most common in older white men. Combined modality therapy including surgery and radiation appears to have a better outcome than each modality alone. When metastatic, agents such as liposomal doxorubicin, paclitaxel and ifosfamide have activity but it is short-lived and not curative...
2017: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/28725430/acute-interstitial-nephritis-after-sequential-ipilumumab-nivolumab-therapy-of-metastatic-melanoma
#4
Lea Bottlaender, Anne-Laure Breton, Louis de Laforcade, Frederique Dijoud, Luc Thomas, Stephane Dalle
BACKGROUND: The anti-Programmed Death receptor 1 (anti-PD-1) antibodies nivolumab and pembrolizumab are new treatments in metastatic melanoma. Immunotherapies are best known to be responsible for thrombotic microangiopathy. However, immune interstitial nephritis has been described in a patient treated by nivolumab and ipilimumab concomitantly, and three cases of granulomatous interstitial nephritis have been reported with ipilimumab monotherapy. We report herein a case of acute interstitial immune nephritis in a patient treated with nivolumab after ipilimumab for pulmonary metastatic melanoma...
2017: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/28724802/partially-exhausted-tumor-infiltrating-lymphocytes-predict-response-to-combination-immunotherapy
#5
Kimberly Loo, Katy K Tsai, Kelly Mahuron, Jacqueline Liu, Mariela L Pauli, Priscila M Sandoval, Adi Nosrati, James Lee, Lawrence Chen, Jimmy Hwang, Lauren S Levine, Matthew F Krummel, Alain P Algazi, Michael D Alvarado, Michael D Rosenblum, Adil I Daud
BACKGROUND: Programmed death 1 (PD-1) inhibition activates partially exhausted cytotoxic T lymphocytes (peCTLs) and induces tumor regression. We previously showed that the peCTL fraction predicts response to anti-PD-1 monotherapy. Here, we sought to correlate peCTL and regulatory T lymphocyte (Treg) levels with response to combination immunotherapy, and with demographic/disease characteristics, in metastatic melanoma patients. METHODS: Pretreatment melanoma samples underwent multiparameter flow cytometric analysis...
July 20, 2017: JCI Insight
https://www.readbyqxmd.com/read/28724377/combination-therapy-for-melanoma-with-braf-mek-inhibitor-and-immune-checkpoint-inhibitor-a-mathematical-model
#6
Xiulan Lai, Avner Friedman
BACKGROUND: The B-raf gene is mutated in up to 66% of human malignant melanomas, and its protein product, BRAF kinase, is a key part of RAS-RAF-MEK-ERK (MAPK) pathway of cancer cell proliferation. BRAF-targeted therapy induces significant responses in the majority of patients, and the combination BRAF/MEK inhibitor enhances clinical efficacy, but the response to BRAF inhibitor and to BRAF/MEK inhibitor is short lived. On the other hand, treatment of melanoma with an immune checkpoint inhibitor, such as anti-PD-1, has lower response rate but the response is much more durable, lasting for years...
July 19, 2017: BMC Systems Biology
https://www.readbyqxmd.com/read/28723893/in-vivo-crispr-screening-identifies-ptpn2-as-a-cancer-immunotherapy-target
#7
Robert T Manguso, Hans W Pope, Margaret D Zimmer, Flavian D Brown, Kathleen B Yates, Brian C Miller, Natalie B Collins, Kevin Bi, Martin W LaFleur, Vikram R Juneja, Sarah A Weiss, Jennifer Lo, David E Fisher, Diana Miao, Eliezer Van Allen, David E Root, Arlene H Sharpe, John G Doench, W Nicholas Haining
Immunotherapy with PD-1 checkpoint blockade is effective in only a minority of patients with cancer, suggesting that additional treatment strategies are needed. Here we use a pooled in vivo genetic screening approach using CRISPR-Cas9 genome editing in transplantable tumours in mice treated with immunotherapy to discover previously undescribed immunotherapy targets. We tested 2,368 genes expressed by melanoma cells to identify those that synergize with or cause resistance to checkpoint blockade. We recovered the known immune evasion molecules PD-L1 and CD47, and confirmed that defects in interferon-γ signalling caused resistance to immunotherapy...
July 19, 2017: Nature
https://www.readbyqxmd.com/read/28716106/acute-interstitial-nephritis-after-sequential-ipilumumab-nivolumab-therapy-of-metastatic-melanoma
#8
Lea Bottlaender, Anne-Laure Breton, Louis de Laforcade, Frederique Dijoud, Luc Thomas, Stephane Dalle
BACKGROUND: The anti-Programmed Death receptor 1 (anti-PD-1) antibodies nivolumab and pembrolizumab are new treatments in metastatic melanoma. Immunotherapies are best known to be responsible for thrombotic microangiopathy. However, immune interstitial nephritis has been described in a patient treated by nivolumab and ipilimumab concomitantly, and three cases of granulomatous interstitial nephritis have been reported with ipilimumab monotherapy. We report herein a case of acute interstitial immune nephritis in a patient treated with nivolumab after ipilimumab for pulmonary metastatic melanoma...
July 18, 2017: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/28716069/angiosarcoma-treated-successfully-with-anti-pd-1-therapy-a-case-report
#9
Simran Sindhu, Lana H Gimber, Lee Cranmer, Ali McBride, Andrew S Kraft
BACKGROUND: Angiosarcomas are tumors of malignant endothelial origin that have a poor prognosis with a five-year survival of less than 40%. These tumors can be found in all age groups, but are more common in older patients; with the cutaneous form most common in older white men. Combined modality therapy including surgery and radiation appears to have a better outcome than each modality alone. When metastatic, agents such as liposomal doxorubicin, paclitaxel and ifosfamide have activity but it is short-lived and not curative...
July 18, 2017: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/28715649/excellent-response-to-anti-pd-1-therapy-in-a-patient-with-hepatocellular-carcinoma-case-report-and-review-of-literature
#10
Hirva Mamdani, Howard Wu, Bert H O'Neil, Amikar Sehdev
Hepatocellular carcinoma (HCC) is an aggressive cancer associated with high mortality worldwide. HCC develops in the setting of underlying cirrhosis due to chronic liver disease. Surgery is usually considered the treatment of choice for early disease; however, most patients have locally advanced or metastatic HCC at diagnosis in which case treatments are limited. Immune checkpoint blockade of programmed death receptor-1 (PD-1) pathway offers a potential treatment strategy based on the encouraging results of the phase I/II trial of nivolumab (Checkmate 040 trial)...
May 2017: Discovery Medicine
https://www.readbyqxmd.com/read/28700789/hair-repigmentation-during-immunotherapy-treatment-with-an-anti-programmed-cell-death-1-and-anti-programmed-cell-death-ligand-1-agent-for-lung-cancer
#11
Noelia Rivera, Aram Boada, M Isabel Bielsa, M Teresa Fernández-Figueras, Enric Carcereny, M Teresa Moran, Carlos Ferrándiz
Importance: New targeted therapies for cancer have been released in recent years, opening new horizons in the treatment of patients with cancer. However, their related adverse events (AE) are not fully characterized. Hair repigmentation (HR) is a nondescribed effect secondary to anti-programmed cell death 1 (anti-PD-1) and anti-programmed cell death ligand 1 (anti-PD-L1 ) therapy for treatment of lung cancer (LC), in opposition to the vitiligo reactions that develop during melanoma treatment...
July 12, 2017: JAMA Dermatology
https://www.readbyqxmd.com/read/28694003/pd-l1-and-immune-escape-insights-from-melanoma-and-other-lineage-unrelated-malignancies
#12
Noah Frydenlund, Meera Mahalingam
One of the major breakthroughs in oncology in the past decade has been the research and development of immune checkpoint inhibitors. Since the discovery of the PD-1/PD-L1 axis as a key mediator in peripheral self-tolerance and the subsequent discovery of its role promoting immune escape in cancers, the PD-1/PD-L1 pathway has produced considerable excitement from both a scientific and therapeutic stand point. The past decade has seen an explosion in the number of clinical trials utilizing antI-PD-1/PD-L1 therapy...
July 7, 2017: Human Pathology
https://www.readbyqxmd.com/read/28693793/biomarkers-of-response-to-pd-1-pd-l1-inhibition
#13
REVIEW
Saman Maleki Vareki, Carmen Garrigós, Ignacio Duran
Immunotherapy is a promising treatment strategy for cancer that has recently shown unprecedented survival benefits in selected patients. A number of immunomodulatory agents that target immune system checkpoints such as the cytotoxic T-lymphocyte antigen 4 (CTLA-4), the programmed death-1 (PD-1) or its ligand (PD-L1), have received regulatory approval for the treatment of multiple cancers including malignant melanoma, non-small cell lung cancer, renal cell carcinoma, classical Hodgkin lymphoma, and recurrent or metastatic head and neck squamous cell carcinoma...
August 2017: Critical Reviews in Oncology/hematology
https://www.readbyqxmd.com/read/28690075/tumor-microenvironment-changes-leading-to-resistance-of-immune-checkpoint-inhibitors-in-metastatic-melanoma-and-strategies-to-overcome-resistance
#14
REVIEW
Bhargavi Pulluri, Abhijeet Kumar, Montaser Shaheen, Joanne Jeter, Srinath Sundararajan
Immunotherapy with checkpoint inhibitors targeting CTLA-4 and/or PD-1 receptors independent of the BRAF mutational status and targeted therapy with BRAF and MEK inhibitors in BRAF V600 mutated patients have taken the forefront of advanced melanoma treatment. The main advantage of immunotherapy is its ability to provide durable responses in a subset of patients. However, significant proportions of patients either do not respond or have progression after initial response to immunotherapies. Multiple changes in the tumor microenvironment, such as down regulation of immune checkpoint ligands by tumor, alteration in interferon signaling, and activation of alternate immune suppressive pathways, have been identified as possible reasons for failure of immune checkpoint therapy...
July 6, 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/28688464/parkinson-disease-and-melanoma-confirming-and-reexamining-an-association
#15
Lauren A Dalvin, Gena M Damento, Barbara P Yawn, Barbara A Abbott, David O Hodge, Jose S Pulido
OBJECTIVE: To examine an association between melanoma and Parkinson disease (PD). PATIENTS AND METHODS: Phase I: Rochester Epidemiology Project records were used to identify (between January 1, 1976, and December 31, 2013) patients with PD in Olmsted County, Minnesota, with 3 matched controls per case. After review, JMP statistical software with logistic regression analysis was used to assess the risk of preexisting melanoma in patients with PD vs controls. Phase II: All Rochester Epidemiology Project cases of melanoma were identified (between January 1, 1976, and December 31, 2014), with 1 control per case...
July 2017: Mayo Clinic Proceedings
https://www.readbyqxmd.com/read/28683958/-adverse-effects-of-immune-checkpoint-inhibitors-used-to-treat-melanoma-and-other-cancer
#16
Claire Jacquin-Porretaz, Charlée Nardin, Eve Puzenat, Blandine Roche-Kubler, François Aubin
Monoclonal antibodies targeted against the immune checkpoint molecules CTLA-4 and PD-1 have recently obtained approval for the treatment of metastatic melanoma and advanced/refractory non small-cell lung cancers and metastatic renal cancer. Besides their efficacy profile, these immune targeted agents also generate immune-related adverse events that may be life threatening if not anticipated and managed appropriately. This new family of dysimmune toxicities remains largely unknown to the broad oncology community...
July 3, 2017: La Presse Médicale
https://www.readbyqxmd.com/read/28681063/circulating-tumour-dna-for-monitoring-treatment-response-to-anti-pd-1-immunotherapy-in-melanoma-patients
#17
Atsuko Ashida, Kaori Sakaizawa, Hisashi Uhara, Ryuhei Okuyama
Anti-programmed cell death-1 (anti-PD-1) antibody shows high therapeutic efficacy in patients with advanced melanoma. However, assessment of its therapeutic activity can be challenging because of tumour enlargement associated with intratumoural inflammation. Because circulating tumour DNA (ctDNA) correlates with tumour burden, we assessed the value of ctDNA levels as an indicator of tumour changes. Quantification of ctDNA (BRAFmutant or NRASmutant) levels by droplet digital PCR in 5 patients with BRAF or NRAS mutant melanoma during the treatment course showed dynamic changes corresponding to radiological and clinical alterations...
July 6, 2017: Acta Dermato-venereologica
https://www.readbyqxmd.com/read/28680759/parallel-profiling-of-immune-infiltrate-subsets-in-uveal-melanoma-versus-cutaneous-melanoma-unveils-similarities-and-differences-a-pilot-study
#18
Yong Qin, Mariana Petaccia de Macedo, Alexandre Reuben, Marie-Andrée Forget, Cara Haymaker, Chantale Bernatchez, Christine N Spencer, Vancheswaran Gopalakrishnan, Sujan Reddy, Zachary A Cooper, Orenthial J Fulbright, Renjith Ramachandran, Arely Wahl, Esteban Flores, Shawne T Thorsen, Rene J Tavera, Claudius Conrad, Michelle D Williams, Michael T Tetzlaff, Wei-Lien Wang, Dan S Gombos, Bita Esmaeli, Rodabe N Amaria, Patrick Hwu, Jennifer A Wargo, Alexander J Lazar, Sapna P Patel
The low response rates to immunotherapy in uveal melanoma (UM) sharply contrast with reputable response rates in cutaneous melanoma (CM) patients. To characterize the mechanisms responsible for resistance to immunotherapy in UM, we performed immune profiling in tumors from 10 metastatic UM patients and 10 metastatic CM patients by immunohistochemistry (IHC). Although there is no difference in infiltrating CD8(+) T cells between UM and CM, a significant decrease in programmed death-1 (PD-1)-positive lymphocytes was observed and lower levels of programmed death ligand-1 (PD-L1) in UM metastases compared with CM metastases...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28679768/pd-1-%C3%A2-polyfunctional-t-cells-dominate-the-periphery-after-tumor-infiltrating-lymphocyte-therapy-for-cancer
#19
Marco Donia, Julie Westerlin Kjeldsen, Rikke Andersen, Marie Christine Wulff Westergaard, Valentina Bianchi, Mateusz Legut, Meriem Attaf, Barbara Szomolay, Sascha Ott, Garry Dolton, Rikke Lyngaa, Sine Reker Hadrup, Andrew K Sewell, Inge Marie Svane
Infusion of highly heterogeneous populations of autologous tumor-infiltrating lymphocytes (TILs) can result in tumor regression of exceptional duration. Initial tumor regression has been associated with persistence of tumor-specific TILs one month after infusion, but mechanisms leading to long-lived memory responses are currently unknown. Here we studied the dynamics of bulk tumor-reactive CD8(+) T cell populations in patients with metastatic melanoma following treatment with TILs. <p>Experimental Design: We analyzed the function and phenotype of tumor-reactive CD8(+) T cells contained in serial blood samples of sixteen patients treated with TILs</p> <p>Results: Polyfunctional tumor-reactive CD8(+) T cells accumulated over time in the peripheral lymphocyte pool...
July 5, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28679300/the-emerging-role-of-immune-checkpoint-based-approaches-in-aml-and-mds
#20
Prajwal Boddu, Hagop Kantarjian, Guillermo Garcia-Manero, James Allison, Padmanee Sharma, Naval Daver
The development of immune checkpoint inhibitors represents a major breakthrough in the field of cancer therapeutics. Pursuant to their success in melanoma and numerous solid tumor malignancies, these agents are being investigated in hematological malignancies including acute myelogenous leukemia (AML) and myelodysplastic syndromes (MDS). Although AML/MDS have traditionally been considered to be less immunogenic than solid tumor malignancies, recent pre-clinical models suggest a therapeutic role for immune checkpoint inhibition in these diseases...
July 6, 2017: Leukemia & Lymphoma
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