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https://www.readbyqxmd.com/read/28229253/the-biology-of-uveal-melanoma
#1
Adriana Amaro, Rosaria Gangemi, Francesca Piaggio, Giovanna Angelini, Gaia Barisione, Silvano Ferrini, Ulrich Pfeffer
Uveal melanoma (UM), a rare cancer of the eye, is distinct from cutaneous melanoma by its etiology, the mutation frequency and profile, and its clinical behavior including resistance to targeted therapy and immune checkpoint blockers. Primary disease is efficiently controlled by surgery or radiation therapy, but about half of UMs develop distant metastasis mostly to the liver. Survival of patients with metastasis is below 1 year and has not improved in decades. Recent years have brought a deep understanding of UM biology characterized by initiating mutations in the G proteins GNAQ and GNA11...
February 22, 2017: Cancer Metastasis Reviews
https://www.readbyqxmd.com/read/28197360/enhancing-the-clinical-coverage-and-anticancer-efficacy-of-immune-checkpoint-blockade-through-manipulation-of-the-gut-microbiota
#2
Jonathan M Pitt, Marie Vétizou, Ivo Gomperts Boneca, Patricia Lepage, Mathias Chamaillard, Laurence Zitvogel
Although anticancer therapy with immune checkpoint blockers has seen unprecedented success, it fails to control neoplasia in most patients and often causes immune-related adverse events (irAEs). Our recent research shows the immunostimulatory and antitumor effects of CTLA-4 blockade depend on distinct Bacteroides species of the gut microbiota, signifying novel approaches to improve such immunotherapies.
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28129791/new-strategies-for-cancer-immunotherapy-targeting-regulatory-t-cells
#3
Francesca Finotello, Zlatko Trajanoski
The immunosuppressive action of regulatory T (Treg) cells is one mechanism attributed to the limited success of cancer immunotherapies with checkpoint blockers. Two recent studies report distinct transcriptional profiles of tumor-infiltrating Treg cells and expression of specific molecules, suggesting novel strategies to overcome resistance to cancer immunotherapy.
January 27, 2017: Genome Medicine
https://www.readbyqxmd.com/read/27911273/robust-detection-of-immune-transcripts-in-ffpe-samples-using-targeted-rna-sequencing
#4
Benjamin E Paluch, Sean T Glenn, Jeffrey M Conroy, Antonios Papanicolau-Sengos, Wiam Bshara, Angela R Omilian, Elizabeth Brese, Mary Nesline, Blake Burgher, Jonathan Andreas, Kunle Odunsi, Kevin Eng, Ji He, Maochun Qin, Mark Gardner, Lorenzo Galluzzi, Carl D Morrison
Current criteria for identifying cancer patients suitable for immunotherapy with immune checkpoint blockers (ICBs) are subjective and prone to misinterpretation, as they mainly rely on the visual assessment of CD274 (best known as PD-L1) expression levels by immunohistochemistry (IHC). To address this issue, we developed a RNA sequencing (RNAseq)-based approach that specifically measures the abundance of immune transcripts in formalin-fixed paraffin embedded (FFPE) specimens. Besides exhibiting superior sensitivity as compared to whole transcriptome RNAseq, our assay requires little starting material, implying that it is compatible with RNA degradation normally caused by formalin...
January 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/27795504/dendritic-cell-and-cancer-immune-checkpoint
#5
Terufumi Kubo, Yoshihiko Hirohashi, Toshihiko Torigoe
  Extensive research over 100 years has clarified that cancers are surely suppressed by human immune system. Unfortunately, a number of clinical trials with various approaches have fallen short of clinical application because of the lack of significant anti-tumor effect. However, recent approved immune checkpoint inhibitors, namely PD-1 and CTLA-4 blockers, provide even better prognosis than existing chemotherapy in patients with certain types of cancer. There is no doubt that immunotherapy is becoming a standard treatment as well as surgery, chemotherapy and radiotherapy...
2016: Nihon Rinshō Men'eki Gakkai Kaishi, Japanese Journal of Clinical Immunology
https://www.readbyqxmd.com/read/27792052/novel-insights-in-the-regulation-and-function-of-macrophages-in-the-tumor-microenvironment
#6
Evangelia Bolli, Kiavash Movahedi, Damya Laoui, Jo A Van Ginderachter
PURPOSE OF REVIEW: Tumors contain not only cancer cells but also nontransformed types of cells, the stromal cells. A bidirectional interplay exists between transformed and nontransformed cells leading to tumor progression and metastasis. Tumor-associated macrophages (TAMs) are the most abundant tumor-infiltrating leukocytes characterized by a high heterogeneity and plasticity. TAMs exhibit strong protumoral activities and are related to bad prognosis and worse overall survival in various cancer types...
January 2017: Current Opinion in Oncology
https://www.readbyqxmd.com/read/27786364/usefulness-of-serum-5-s-cysteinyl-dopa-as-a-biomarker-for-predicting-prognosis-and-detecting-relapse-in-patients-with-advanced-stage-malignant-melanoma
#7
Hiroshi Umemura, Osamu Yamasaki, Tatsuya Kaji, Masaki Otsuka, Kenji Asagoe, Minoru Takata, Keiji Iwatsuki
With the recent development of novel molecular targeted drugs for advanced stage malignant melanoma (MM), including RAF and mitogen-activated protein kinase kinase inhibitors and immune checkpoint blockers, the early detection of relapse is important for managing patients with MM. In this study, we retrospectively analyzed two conventional serum biomarkers, 5-S-cysteinyl-dopa and lactate dehydrogenase, in patients with MM (n = 140) who were treated at a single Japanese institute from June 2007 to June 2015...
October 27, 2016: Journal of Dermatology
https://www.readbyqxmd.com/read/27764686/concurrent-irradiation-with-the-anti-programmed-cell-death-ligand-1-immune-checkpoint-blocker-durvalumab-single-centre-subset-analysis-from-a-phase-1-2-trial
#8
Antonin Levy, Christophe Massard, Jean-Charles Soria, Eric Deutsch
PURPOSE: To assess preliminary safety and efficacy results of the anti-programmed cell death ligand-1 (anti-PD-L1) durvalumab in combination with radiotherapy (RT) in an expansion cohort of patients included in a phase 1/2 trial at our institution. PATIENTS AND METHODS: Data from patients who received concurrent palliative RT with durvalumab (10 mg/kg every 2 weeks via intravenous infusion) were analysed in terms of safety (CTCAE v4.0) and efficacy (RECIST v1.1 and tumour growth rate [TGR])...
November 2016: European Journal of Cancer
https://www.readbyqxmd.com/read/27757313/trial-watch-immunotherapy-plus-radiation-therapy-for-oncological-indications
#9
REVIEW
Erika Vacchelli, Norma Bloy, Fernando Aranda, Aitziber Buqué, Isabelle Cremer, Sandra Demaria, Alexander Eggermont, Silvia Chiara Formenti, Wolf Hervé Fridman, Jitka Fucikova, Jérôme Galon, Radek Spisek, Eric Tartour, Laurence Zitvogel, Guido Kroemer, Lorenzo Galluzzi
Malignant cells succumbing to some forms of radiation therapy are particularly immunogenic and hence can initiate a therapeutically relevant adaptive immune response. This reflects the intrinsic antigenicity of malignant cells (which often synthesize a high number of potentially reactive neo-antigens) coupled with the ability of radiation therapy to boost the adjuvanticity of cell death as it stimulates the release of endogenous adjuvants from dying cells. Thus, radiation therapy has been intensively investigated for its capacity to improve the therapeutic profile of several anticancer immunotherapies, including (but not limited to) checkpoint blockers, anticancer vaccines, oncolytic viruses, Toll-like receptor (TLR) agonists, cytokines, and several small molecules with immunostimulatory effects...
2016: Oncoimmunology
https://www.readbyqxmd.com/read/27750242/clinical-significance-of-epigenetic-alterations-in-human-hepatocellular-carcinoma-and-its-association-with-genetic-mutations
#10
REVIEW
Naoshi Nishida, Masatoshi Kudo
Accumulation of genetic and epigenetic alterations is a hallmark of cancer genomes, including those in hepatocellular carcinoma (HCC). Particularly, in human HCC, epigenetic changes are more frequently observed than genetic changes in a variety of cancer-related genes, suggesting a potential role for epigenetic alterations during hepatocarcinogenesis. Several environmental factors, such as inflammation, obesity, and steatosis, are reported to affect the epigenetic status in hepatocytes, which could play a role in HCC development...
2016: Digestive Diseases
https://www.readbyqxmd.com/read/27687979/mouse-models-in-oncoimmunology
#11
Laurence Zitvogel, Jonathan M Pitt, Romain Daillère, Mark J Smyth, Guido Kroemer
Fundamental cancer research and the development of efficacious antineoplastic treatments both rely on experimental systems in which the relationship between malignant cells and immune cells can be studied. Mouse models of transplantable, carcinogen-induced or genetically engineered malignancies - each with their specific advantages and difficulties - have laid the foundations of oncoimmunology. These models have guided the immunosurveillance theory that postulates that evasion from immune control is an essential feature of cancer, the concept that the long-term effects of conventional cancer treatments mostly rely on the reinstatement of anticancer immune responses and the preclinical development of immunotherapies, including currently approved immune checkpoint blockers...
December 2016: Nature Reviews. Cancer
https://www.readbyqxmd.com/read/27680009/-cutaneous-squamous-cell-carcinoma
#12
REVIEW
U Leiter, R Gutzmer, M Alter, C Ulrich, A S Lonsdorf, M M Sachse, U Hillen
Squamous cell carcinoma (SCC) of the skin accounts for 20 % of non-melanoma skin cancer and is one of the most frequent types of cancer in Caucasian populations. Diagnosis is based on the clinical features and should be histopathologically confirmed to adequately address the prognosis and treatment. Complete surgical excision with histopathological control of excision margins is the gold standard in the treatment of primary SCC. Sentinel lymph node biopsies (SLNB) can be considered in SCC with a tumor thickness of >6 mm but there is currently no evidence concerning prognostic and therapeutic effects...
November 2016: Der Hautarzt; Zeitschrift Für Dermatologie, Venerologie, und Verwandte Gebiete
https://www.readbyqxmd.com/read/27651308/efficacy-of-cotargeting-angiopoietin-2-and-the-vegf-pathway-in-the-adjuvant-postsurgical-setting-for-early-breast-colorectal-and-renal-cancers
#13
Florence T H Wu, Shan Man, Ping Xu, Annabelle Chow, Marta Paez-Ribes, Christina R Lee, Steven R Pirie-Shepherd, Urban Emmenegger, Robert S Kerbel
Antiangiogenic tyrosine kinase inhibitors (TKI) that target VEGF receptor-2 (VEGFR2) have not been effective as adjuvant treatments for micrometastatic disease in phase III clinical trials. Angiopoietin-2 (Ang2) is a proangiogenic and proinflammatory vascular destabilizer that cooperates with VEGF. The purpose of this study was to test whether CVX-060 (an Ang2-specific CovX-body) can be combined with VEGFR2-targeting TKIs (sunitinib or regorafenib) to successfully treat postsurgical metastatic disease in multiple orthotopically implanted human tumor xenograft and syngeneic murine tumor models...
December 1, 2016: Cancer Research
https://www.readbyqxmd.com/read/27614165/checkpoint-inhibitors-in-chronic-kidney-failure-and-an-organ-transplant-recipient
#14
Saskia Herz, Thomas Höfer, Matina Papapanagiotou, Julia Christina Leyh, Sarah Meyenburg, Dirk Schadendorf, Selma Ugurel, Alexander Roesch, Elisabeth Livingstone, Bastian Schilling, Cindy Franklin
BACKGROUND: Immune-checkpoint inhibitors have been approved for the treatment of metastatic melanoma based on several phase III trials. Patients after organ transplantation and patients with impaired renal function were excluded from these studies. Recently, allograft rejections were reported in organ transplant recipients receiving PD-1 blocking antibodies. PATIENTS AND FINDINGS: Four patients with metastatic melanoma and impaired kidney function (baseline serum creatinine 1...
November 2016: European Journal of Cancer
https://www.readbyqxmd.com/read/27599426/ips-cell-derived-dendritic-cells-and-macrophages-for-cancer-therapy
#15
Satoru Senju
Antibody-based anti-cancer immunotherapy was recently recognized as one of the truly effective therapies for cancer patients. Antibodies against cell surface cancer antigens, such as CD20, and also those against immune-inhibitory molecules called "immune checkpoint blockers", such as CTLA4 or PD1, have emerged. Large-scale clinical trials have confirmed that, in some cases, antibody-based drugs are superior to conventional chemotherapeutic agents. These antibody-based drugs are now being manufactured employing a mass-production system by pharmaceutical companies...
August 2016: [Rinshō Ketsueki] the Japanese Journal of Clinical Hematology
https://www.readbyqxmd.com/read/27539246/emerging-monoclonal-antibodies-for-the-treatment-of-renal-cell-carcinoma-rcc
#16
Michael B Atkins, George K Philips
INTRODUCTION: Advanced renal cell carcinoma (RCC) was considered refractory to most cancer therapies until the 1980s, after which immune modulating agents and targeted agents were developed. Recently the rapid development of therapeutic monoclonal antibodies targeting immune checkpoint pathways has provided significant clinical benefit in patients with many distinct cancer types. Nivolumab, an anti-PD1 monoclonal antibody showed improvement in response rate and overall survival in patients with previously treated RCC and received US FDA approval in late 2015...
September 2016: Expert Opinion on Emerging Drugs
https://www.readbyqxmd.com/read/27512141/inhibition-of-bcl-xl-sensitizes-cells-to-mitotic-blockers-but-not-mitotic-drivers
#17
Ailsa Bennett, Olivia Sloss, Caroline Topham, Louisa Nelson, Anthony Tighe, Stephen S Taylor
Cell fate in response to an aberrant mitosis is governed by two competing networks: the spindle assembly checkpoint (SAC) and the intrinsic apoptosis pathway. The mechanistic interplay between these two networks is obscured by functional redundancy and the ability of cells to die either in mitosis or in the subsequent interphase. By coupling time-lapse microscopy with selective pharmacological agents, we systematically probe pro-survival Bcl-xL in response to various mitotic perturbations. Concentration matrices show that BH3-mimetic-mediated inhibition of Bcl-xL synergises with perturbations that induce an SAC-mediated mitotic block, including drugs that dampen microtubule dynamics, and inhibitors targeting kinesins and kinases required for spindle assembly...
August 2016: Open Biology
https://www.readbyqxmd.com/read/27501841/the-spectrum-of-serious-infections-among-patients-receiving-immune-checkpoint-blockade-for-the-treatment-of-melanoma
#18
Maria Del Castillo, Fabian A Romero, Esther Argüello, Chrisann Kyi, Michael A Postow, Gil Redelman-Sidi
The risk of infection among patients receiving immune checkpoint blockade is unknown. We retrospectively reviewed medical records of 740 patients with melanoma who received immune checkpoint blockers. Serious infection occurred in 54 patients (7.3%). The main risk factors were receipt of corticosteroids and/or infliximab.
December 1, 2016: Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America
https://www.readbyqxmd.com/read/27495145/immune-modulation-by-hypofractionated-stereotactic-radiation-therapy-therapeutic-implications
#19
REVIEW
Ilinca Popp, Anca Ligia Grosu, Gabriele Niedermann, Dan G Duda
Stereotactic body radiation therapy (SBRT) has become an attractive treatment modality and a safe, non-invasive alternative to surgery to control primary or secondary malignant tumors. While emphasis has been on the local tumor control as a treatment objective for SBRT, the rare but intriguing observations of abscopal (or out-of-field) effects have pointed to the exciting possibility of activating anti-tumor immunity by using high-dose radiation. This review summarizes the available evidence supporting immune modulation by SBRT alone, as well as its potential combination with immunotherapy...
August 2016: Radiotherapy and Oncology: Journal of the European Society for Therapeutic Radiology and Oncology
https://www.readbyqxmd.com/read/27494973/-not-available
#20
REVIEW
Christine Mateus, Cristina Libenciuc, Caroline Robert
ANTI-PD1 ROLE IN TREATMENT OF CUTANEOUS MELANOMA: The treatment of metastatic melanoma dramatically changed over the last years. Two therapeutic revolutions emerged in parallel, targeted anti-BRAF and anti-MEK therapies, for patients BRAFV600 mutated and immunotherapy with immune checkpoint blockers using anti-CTLA-4 then anti-PD1 monoclonal antibodies. Indeed, melanoma immunotherapy was a golden objective for many years but in spite of important efforts using cytokines (interferon, interleukin) and different vaccine approaches no objective improvement of patients 'prognosis was obtained...
June 2016: Bulletin du Cancer
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