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https://www.readbyqxmd.com/read/27742386/the-bad-and-the-good-news-on-cancer-immunotherapy-implications-for-organ-transplant-recipients
#1
Umberto Maggiore, Julio Pascual
Cancer immunotherapy, especially the use of checkpoint inhibitors, is expanding and can be efficacious in organ transplant recipients with malignant neoplasia. In this review, we summarize clinical findings and evolution of several patients treated with CTL4-4 or PD-1 inhibitors reported in the literature. The CTL-4 inhibitor ipilimumab has been safely used in several liver and kidney allograft recipients. PD1-inhibitors look promising for tumor shrinking, but acute rejection is the rule, so they should be avoided in recipients of life-saving organs...
September 2016: Advances in Chronic Kidney Disease
https://www.readbyqxmd.com/read/27645905/identification-of-langerhans-like-cells-in-the-immunocompetent-tissues-of-channel-catfish-ictalurus-punctatus
#2
Adef O Kordon, Matthew A Scott, Iman Ibrahim, Hossam Abdelhamed, Hamada Ahmed, Wes Baumgartner, Attila Karsi, Lesya M Pinchuk
Dendritic cells (DCs) are the most powerful antigen presenting cells (APCs) that have a critical role in bridging innate and adaptive immune responses in vertebrates. Dendritic cells have been characterized morphologically and functionally in the teleost fish models such as rainbow trout, salmonids, medaka, and zebrafish. The presence of DCs with remarkable similarities to human Langerhans cells (LCs) has been described in the spleen and anterior kidney of salmonids and rainbow trout. However, there is no evidence of the presence of DCs and their role in channel catfish immunity...
September 16, 2016: Fish & Shellfish Immunology
https://www.readbyqxmd.com/read/27622074/carcinogenesis-of-renal-cell-carcinoma-reflected-in-hla-ligands-a-novel-approach-for-synergistic-peptide-vaccination-design
#3
Martin G Klatt, Daniel J Kowalewski, Heiko Schuster, Moreno Di Marco, Jörg Hennenlotter, Arnulf Stenzl, Hans-Georg Rammensee, Stefan Stevanović
Despite recent advances in immunotherapy of renal cell carcinoma (RCC), peptide vaccination strategies still lack an approach for personalized peptide vaccination that takes intra- and inter-tumoral heterogeneity and biological characteristics into account. In this study, we use an immunoprecipitation and mass spectrometry-based approach supplemented by network analysis of HLA ligands to target this goal. By analyzing HLA-presented peptides for HLA class I and II of 11 malignant and 6 non-malignant kidney tissue samples, more than 2,700 peptides and 1,600 corresponding source proteins were identified...
August 2016: Oncoimmunology
https://www.readbyqxmd.com/read/27584025/cancer-immunotherapy-new-applications-in-urologic-oncology
#4
Michael E Hurwitz, Joseph Sokhn, Daniel P Petrylak
PURPOSE OF REVIEW: Over the last 10 years, harnessing of the immune system to attack tumors has been one of the major breakthroughs in cancer, primarily through the use of immune checkpoint inhibitors (ICIs). This review will summarize current immune treatments in urologic malignancies and ongoing trials with novel combinations and in different disease settings. RECENT FINDINGS: Patients with urologic malignancies such as kidney and bladder cancer have benefited significantly from these advances with the approval of ICIs in both of these diseases...
November 2016: Current Opinion in Urology
https://www.readbyqxmd.com/read/27572319/inhibiting-tryptophan-metabolism-enhances-interferon-therapy-in-kidney-cancer
#5
Josephine F Trott, Jeffrey Kim, Omran Abu Aboud, Hiromi Wettersten, Benjamin Stewart, Grace Berryhill, Francisco Uzal, Russell C Hovey, Ching-Hsien Chen, Katie Anderson, Ashley Graef, Aaron L Sarver, Jaime F Modiano, Robert H Weiss
Renal cell carcinoma (RCC) is increasing in incidence, and a complete cure remains elusive. While immune-checkpoint antibodies are promising, interferon-based immunotherapy has been disappointing. Tryptophan metabolism, which produces immunosuppressive metabolites, is enhanced in RCC. Here we show indolamine-2,3-dioxygenase-1 (IDO1) expression, a kynurenine pathway enzyme, is increased not only in tumor cells but also in the microenvironment of human RCC compared to normal kidney tissues. Neither kynurenine metabolites nor IDO inhibitors affected the survival or proliferation of human RCC or murine renal cell adenocarcinoma (RENCA) cells in vitro...
August 27, 2016: Oncotarget
https://www.readbyqxmd.com/read/27569040/biennial-report-on-genitourinary-cancers
#6
Karim Fizazi
The last 2 years (2014 and 2015) have witnessed major advances in the treatment of genitourinary malignancies. Of note and in marked contrast to previous years, all four major cancers (prostate cancer, testicular cancer, kidney cancer, and bladder cancer) have benefited from this progress. In prostate cancer, it was clearly demonstrated that a local treatment should be administered for high-risk localised disease. The standard of care was changed for patients with upfront metastatic disease with combined androgen deprivation therapy plus docetaxel becoming the new standard for fit patients with multiple bony metastases...
October 2016: European Journal of Cancer
https://www.readbyqxmd.com/read/27565924/drug-induced-myocarditis-after-nivolumab-treatment-in-a-patient-with-pdl1-negative-squamous-cell-carcinoma-of-the-lung
#7
H Semper, F Muehlberg, J Schulz-Menger, M Allewelt, C Grohé
Immunotherapy such as nivolumab is a new promising therapeutic option for advanced stage non small cell lung cancer (NSCLC). Due to the interference with the immune system previously unknown side effects are observed both in clinical studies and experience. Autoimmune phenomena effecting skin, gastrointestinal tract, endocrine glands, kidney and lung have been described. Up to now there is only limited information regarding potential cardiac side effects. We present a case of symptomatic drug induced myocarditis after nine cycles of nivolumab in a patient with efficient anticancer response...
September 2016: Lung Cancer: Journal of the International Association for the Study of Lung Cancer
https://www.readbyqxmd.com/read/27563659/toxicity-management-of-immunotherapy-for-patients-with-metastatic-melanoma
#8
REVIEW
Helena Linardou, Helen Gogas
Checkpoint inhibitors have revolutionized the treatment of patients with metastatic melanoma offering improved responses and significant survival benefit. These agents are now approved for the treatment of metastatic melanoma, squamous and non-squamous non-small cell lung cancer (NSCLC) and kidney cancer, while they are now being investigated in a range of other malignancies. In addition, another anti-PD-L1 monoclonal antibody (atezolizumab) was recently approved for urothelial cancer. Ipilimumab, an anti-cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) antibody and the anti-PD-1 agents nivolumab and pembrolizumab have followed large clinical development programs, therefore, information regarding their safety and toxicity profile is readily available...
July 2016: Annals of Translational Medicine
https://www.readbyqxmd.com/read/27558513/a-one-health-overview-facilitating-advances-in-comparative-medicine-and-translational-research
#9
Cheryl Stroud, Igor Dmitriev, Elena Kashentseva, Jeffrey N Bryan, David T Curiel, Hans Rindt, Carol Reinero, Carolyn J Henry, Philip J Bergman, Nicola J Mason, Josephine S Gnanandarajah, Julie B Engiles, Falon Gray, Danielle Laughlin, Anita Gaurnier-Hausser, Anu Wallecha, Margie Huebner, Yvonne Paterson, Daniel O'Connor, Laura S Treml, James P Stannard, James L Cook, Marc Jacobs, Gerald J Wyckoff, Lee Likins, Ubadah Sabbagh, Andrew Skaff, Amado S Guloy, Harlen D Hays, Amy K LeBlanc, Joan R Coates, Martin L Katz, Leslie A Lyons, Gayle C Johnson, Gary S Johnson, Dennis P O'Brien, Dongsheng Duan, James P Calvet, Barbara Gandolfi, David A Baron, Mark L Weiss, Debra A Webster, Francis N Karanu, Edward J Robb, Robert J Harman
A1 One health advances and successes in comparative medicine and translational researchCheryl StroudA2 Dendritic cell-targeted gorilla adenoviral vector for cancer vaccination for canine melanomaIgor Dmitriev, Elena Kashentseva, Jeffrey N. Bryan, David T. CurielA3 Viroimmunotherapy for malignant melanoma in the companion dog modelJeffrey N. Bryan, David Curiel, Igor Dmitriev, Elena Kashentseva, Hans Rindt, Carol Reinero, Carolyn J. HenryA4 Of mice and men (and dogs!): development of a commercially licensed xenogeneic DNA vaccine for companion animals with malignant melanomaPhilip J...
August 2016: Clinical and Translational Medicine
https://www.readbyqxmd.com/read/27549193/comprehensive-analyses-of-tumor-immunity-implications-for-cancer-immunotherapy
#10
Bo Li, Eric Severson, Jean-Christophe Pignon, Haoquan Zhao, Taiwen Li, Jesse Novak, Peng Jiang, Hui Shen, Jon C Aster, Scott Rodig, Sabina Signoretti, Jun S Liu, X Shirley Liu
BACKGROUND: Understanding the interactions between tumor and the host immune system is critical to finding prognostic biomarkers, reducing drug resistance, and developing new therapies. Novel computational methods are needed to estimate tumor-infiltrating immune cells and understand tumor-immune interactions in cancers. RESULTS: We analyze tumor-infiltrating immune cells in over 10,000 RNA-seq samples across 23 cancer types from The Cancer Genome Atlas (TCGA). Our computationally inferred immune infiltrates associate much more strongly with patient clinical features, viral infection status, and cancer genetic alterations than other computational approaches...
August 22, 2016: Genome Biology
https://www.readbyqxmd.com/read/27533501/immunotherapy-in-kidney-cancer-the-past-present-and-future
#11
Hans Hammers
PURPOSE OF REVIEW: Kidney cancer, in particular clear cell renal cell carcinoma (ccRCC) has long been considered to be sensitive to immunotherapies. With the recent breakthroughs in immunotherapy for solid tumors and the recent approval of the first immune checkpoint inhibitor for ccRCC, we are reviewing the history of immunotherapy in kidney cancer, describing its current state and look into the future of a rapidly evolving landscape in immunotherapy for kidney cancer. RECENT FINDINGS: Systemic treatment options over the past decade have been dominated by targeted therapies inhibiting the vascular endothelial growth factor (VEGF) and mammalian target of rapamycin (mTOR) pathways...
November 2016: Current Opinion in Urology
https://www.readbyqxmd.com/read/27533500/immunotherapy-for-prostate-cancer-is-prostate-an-immune-responsive-tumor
#12
Susan F Slovin
PURPOSE OF REVIEW: The purpose of this review is to identify possible reasons why prostate cancer suboptimally responds to immune therapies. RECENT FINDINGS: Interrogation of the intraprostatic milieu suggests that within the normal prostate, foci of tumor can be surrounded by inflammatory cells that may or may not represent foci of immune sensitivity. Whether or not these cells are specific 'immune responders' depends on a multiplicity of factors within the host and intratumoral/stromal milieu...
November 2016: Current Opinion in Urology
https://www.readbyqxmd.com/read/27521108/checkmate-kidney-injury-associated-with-targeted-cancer-immunotherapy
#13
Mark A Perazella
Immune checkpoint inhibitors are a class of drugs that utilizes immunotherapy to target various cancers. Included are the anti-CTLA-4 and anti-PD-1 receptor antibodies. By reprogramming the immune system, these agents provide a therapy that destroys cancer cells. However, this approach runs the risk of allowing pathologic autoimmunity and organ injury to develop. Unsurprisingly, immune-related adverse effects are described including pneumonitis, colitis, and various endocrinopathies. Now added to this list is AKI, primarily due to ATIN...
September 2016: Kidney International
https://www.readbyqxmd.com/read/27517637/combination-immunotherapy-in-genitourinary-malignancies
#14
Jean Hoffman-Censits, Lindsay Wilde
PURPOSE OF REVIEW: Combination immunotherapy has already shown promise in several tumor types, such as melanoma and nonsmall cell lung cancer, and studies are ongoing to evaluate this approach in other malignancies. Trials such as these will only continue to expand as additional immune therapies are shown to have efficacy as single agents in cancer. The purpose of this review is to outline the current landscape of immunotherapy in genitourinary cancer, and to highlight ongoing and pending combination immunotherapy trials in bladder, kidney, and prostate cancers...
November 2016: Current Opinion in Urology
https://www.readbyqxmd.com/read/27367472/a-difficult-decision-atypical-jc-polyomavirus-encephalopathy-in-a-kidney-transplant-recipient
#15
Seweryn Bialasiewicz, Gareth Hart, Kimberly Oliver, Shruti P Agnihotri, Igor J Koralnik, Raphael Viscidi, Michael D Nissen, Theo P Sloots, Michael T Burke, Nicole M Isbel, John Burke
BACKGROUND: A number of cerebral manifestations are associated with JC polyomavirus (JCPyV) which are diagnosed by detection of JCPyV in cerebrospinal fluid (CSF), often with the support of cerebral imaging. Here we present an unusual case of a kidney transplant patient presenting with progressive neurological deterioration attributed to JCPyV encephalopathy. METHODS: Quantitative polymerase chain reaction JCPyV was used prospectively and retrospectively to track the viral load within the patient blood, urine, CSF, and kidney sections...
June 30, 2016: Transplantation
https://www.readbyqxmd.com/read/27349989/inactivated-mesenchymal-stem-cells-maintain-immunomodulatory-capacity
#16
Franka Luk, Samantha F H de Witte, Sander S Korevaar, Marieke Roemeling-van Rhijn, Marcella Franquesa, Tanja Strini, Sandra van den Engel, Madhusudhana Gargesha, Debashish Roy, Frank J M F Dor, Edwin M Horwitz, Ron W F de Bruin, Michiel G H Betjes, Carla C Baan, Martin J Hoogduijn
Mesenchymal stem cells (MSC) are studied as a cell therapeutic agent for treatment of various immune diseases. However, therapy with living culture-expanded cells comes with safety concerns. Furthermore, development of effective MSC immunotherapy is hampered by lack of knowledge of the mechanisms of action and the therapeutic components of MSC. Such knowledge allows better identification of diseases that are responsive to MSC treatment, optimization of the MSC product, and development of therapy based on functional components of MSC...
September 15, 2016: Stem Cells and Development
https://www.readbyqxmd.com/read/27306502/a-multidisciplinary-approach-to-toxicity-management-of-modern-immune-checkpoint-inhibitors-in-cancer-therapy
#17
Lisa Kottschade, Adam Brys, Tobias Peikert, Mabel Ryder, Laura Raffals, Jerry Brewer, Paul Mosca, Svetomir Markovic
Immune-related Adverse Events (irAEs) are the most significant toxicities associated with the use of checkpoint inhibitors, and result from disinhibition of the host's immune homeostasis. The adverse effects experienced from immunotherapy are significantly different from those of chemotherapy and, to a lesser extent, targeted therapy. Early recognition and diagnosis of these toxicities is often challenging, but is critically important because of the potentially life-threatening nature and associated morbidity...
October 2016: Melanoma Research
https://www.readbyqxmd.com/read/27282937/clinicopathological-features-of-acute-kidney-injury-associated-with-immune-checkpoint-inhibitors
#18
Frank B Cortazar, Kristen A Marrone, Megan L Troxell, Kenneth M Ralto, Melanie P Hoenig, Julie R Brahmer, Dung T Le, Evan J Lipson, Ilya G Glezerman, Jedd Wolchok, Lynn D Cornell, Paul Feldman, Michael B Stokes, Sarah A Zapata, F Stephen Hodi, Patrick A Ott, Michifumi Yamashita, David E Leaf
Immune checkpoint inhibitors (CPIs), monoclonal antibodies that target inhibitory receptors expressed on T cells, represent an emerging class of immunotherapy used in treating solid organ and hematologic malignancies. We describe the clinical and histologic features of 13 patients with CPI-induced acute kidney injury (AKI) who underwent kidney biopsy. Median time from initiation of a CPI to AKI was 91 (range, 21 to 245) days. Pyuria was present in 8 patients, and the median urine protein to creatinine ratio was 0...
September 2016: Kidney International
https://www.readbyqxmd.com/read/27278998/establishment-and-characterization-of-a-highly-immunogenic-human-renal-carcinoma-cell-line
#19
Clelia Prattichizzo, Margherita Gigante, Paola Pontrelli, Alessandro Stella, Maria Teresa Rocchetti, Maddalena Gigante, Eugenio Maiorano, Wolfgang Herr, Michele Battaglia, Loreto Gesualdo, Elena Ranieri
Renal cell carcinoma (RCC) is the most common kidney cancer, and accounts for ~3% of all adult malignancies. RCC has proven refractory to conventional treatment modalities but appears to be the only histological form that shows any consistent response to immunotherapeutic approaches. The development of a clinically effective vaccine remains a major strategic target for devising active specific immunotherapy in RCC. We aimed to identify a highly immunogenic antigenic format for immunotherapeutic approaches, so as to boost immune responses in RCC patients...
August 2016: International Journal of Oncology
https://www.readbyqxmd.com/read/27267608/pembrolizumab-for-patients-with-melanoma-or-non-small-cell-lung-cancer-and-untreated-brain-metastases-early-analysis-of-a-non-randomised-open-label-phase-2-trial
#20
Sarah B Goldberg, Scott N Gettinger, Amit Mahajan, Anne C Chiang, Roy S Herbst, Mario Sznol, Apostolos John Tsiouris, Justine Cohen, Alexander Vortmeyer, Lucia Jilaveanu, James Yu, Upendra Hegde, Stephanie Speaker, Matthew Madura, Amanda Ralabate, Angel Rivera, Elin Rowen, Heather Gerrish, Xiaopan Yao, Veronica Chiang, Harriet M Kluger
BACKGROUND: Immunotherapy targeting the PD-1 axis has activity in several tumour types. We aimed to establish the activity and safety of the PD-1 inhibitor pembrolizumab in patients with untreated brain metastases from melanoma or non-small-cell lung cancer (NSCLC). METHODS: In this non-randomised, open-label, phase 2 trial, we enrolled patients aged 18 years or older with melanoma or NSCLC with untreated brain metastases from the Yale Cancer Center. Patients had at least one untreated or progressive brain metastasis between 5 and 20 mm in diameter without associated neurological symptoms or the need for corticosteroids...
July 2016: Lancet Oncology
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