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https://www.readbyqxmd.com/read/29455872/-pd-l1-expression-and-pd-1-pd-l1-inhibitors-in-breast-cancer
#1
REVIEW
Audrey Monneur, Anthony Gonçalves, François Bertucci
The development of immune checkpoints inhibitors represents one of the major recent advances in oncology. Monoclonal antibodies directed against the programmed cell death protein 1 (PD-1) or its ligand (PD-L1) provides durable disease control, particularly in melanoma, lung, kidney, bladder and head and neck cancers. The purpose of this review is to synthesize current data on the expression of PD-L1 in breast cancer and on the preliminary clinical results of PD-1/PD-L1 inhibitors in breast cancer patients. In breast cancer, PD-L1 expression is heterogeneous and is generally associated with the presence of tumor-infiltrating lymphocytes as well as the presence of poor-prognosis factors, such as young age, high grade, ER-negativity, PR-negativity, and HER-2 overexpression, high proliferative index, and aggressive molecular subtypes (triple negative, basal-like, HER-2-overexpressing)...
February 15, 2018: Bulletin du Cancer
https://www.readbyqxmd.com/read/29455266/inflammatory-tenosynovitis-and-enthesitis-induced-by-immune-checkpoint-inhibitor-treatment
#2
Jun Inamo, Yuko Kaneko, Tsutomu Takeuchi
Reports about immune-related adverse events (IrAEs) induced by immune checkpoint inhibitors (ICIs) have been increasing. Although the importance of understanding joint involvement and myalgia as an IrAE has grown, little is known about its characteristics. The aim of this study was to investigate the incidence and clinical characteristics of articular IrAEs. We reviewed 133 patients who were treated with ICIs in our institution and referred to our rheumatologic. Among them, 2 (1.5%) developed arthritis during the use of anti-PD-1 inhibitor, and there was one patient with joint pain after anti-PD-L1 inhibitor who was referred to our department from another institution...
February 17, 2018: Clinical Rheumatology
https://www.readbyqxmd.com/read/29454155/immune-checkpoint-inhibitors-in-non-small-cell-lung-cancer-nsclc-approaches-on-special-subgroups-and-unresolved-burning-questions
#3
REVIEW
J Remon, N Vilariño, N Reguart
Immune checkpoint inhibitors (ICIs) have been incorporated in the treatment strategy of advanced non-small cell lung cancer (NSCLC). Beyond the already approved indications in first- and second-line setting of advanced NSCLC, new data has recently emerged demonstrating its efficacy in locally advanced disease as maintenance after chemo-radiotherapy and currently several trials are also exploring its efficacy in earlier stages of the disease to evaluate whether these results could be extrapolated to the adjuvant setting...
February 8, 2018: Cancer Treatment Reviews
https://www.readbyqxmd.com/read/29453278/molecular-signatures-of-circulating-melanoma-cells-for-monitoring-early-response-to-immune-checkpoint-therapy
#4
Xin Hong, Ryan J Sullivan, Mark Kalinich, Tanya Todorova Kwan, Anita Giobbie-Hurder, Shiwei Pan, Joseph A LiCausi, John D Milner, Linda T Nieman, Ben S Wittner, Uyen Ho, Tianqi Chen, Ravi Kapur, Donald P Lawrence, Keith T Flaherty, Lecia V Sequist, Sridhar Ramaswamy, David T Miyamoto, Michael Lawrence, Mehmet Toner, Kurt J Isselbacher, Shyamala Maheswaran, Daniel A Haber
A subset of patients with metastatic melanoma have sustained remissions following treatment with immune checkpoint inhibitors. However, analyses of pretreatment tumor biopsies for markers predictive of response, including PD-1 ligand (PD-L1) expression and mutational burden, are insufficiently precise to guide treatment selection, and clinical radiographic evidence of response on therapy may be delayed, leading to some patients receiving potentially ineffective but toxic therapy. Here, we developed a molecular signature of melanoma circulating tumor cells (CTCs) to quantify early tumor response using blood-based monitoring...
February 16, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29449897/atezolizumab-feasible-second-line-therapy-for-patients-with-non-small-cell-lung-cancer-a-review-of-efficacy-safety-and-place-in-therapy
#5
REVIEW
Fanny Jean, Pascale Tomasini, Fabrice Barlesi
Advanced non-small cell lung cancer (NSCLC) prognosis is still poor and has recently been reformed by the development of immune checkpoint inhibitors and the approval of anti-PD-1 (programmed cell-death 1) treatments such as nivolumab and pembrolizumab in second line. More recently, atezolizumab (MDPL 3280A), a programmed cell-death-ligand 1 (PD-L1) inhibitor, was also studied in this setting. Here, we report a review of the literature assessing the efficacy, safety, and place of atezolizumab in the second-line treatment of advanced NSCLC...
December 2017: Therapeutic Advances in Medical Oncology
https://www.readbyqxmd.com/read/29448849/development-of-small-molecule-immune-checkpoint-inhibitors-of-pd-1-pd-l1-as-a-new-therapeutic-strategy-for-tumour-immunotherapy
#6
Kui Li, Tian Hongqi
Cancer immunotherapy has been increasingly utilized to treat advanced malignancies. The signalling network of immune checkpoints has attracted considerable attention. Immune checkpoint inhibitors are revolutionizing the treatment options and expectations for patients with cancer. The reported clinical success of targeting the T-cell immune checkpoint receptors PD-1/PD-L1 has demonstrated the importance of immune modulation. Indeed, antibodies binding to PD-1 or PD-L1 have shown remarkable efficacy. However, antibody drugs have many disadvantages, such as their production cost, stability, and immunogenicity, and therefore, small-molecule inhibitors of PD-1 and its ligand PD-L1 are being introduced...
February 16, 2018: Journal of Drug Targeting
https://www.readbyqxmd.com/read/29444918/immunotherapy-a-new-standard-of-care-in-thoracic-malignancies-a-summary-of-the-european-respiratory-society-research-seminar-of-the-thoracic-oncology-assembly
#7
Adrien Costantini, Marta Grynovska, Francesca Lucibello, Jorge Moisés, Franck Pagès, Ming S Tsao, Frances A Shepherd, Hasna Bouchaab, Marina Garassino, Joachim G J V Aerts, Julien Mazières, Michele Mondini, Thierry Berghmans, Anne-Pascale Meert, Jacques Cadranel
In May 2017, the second European Respiratory Society research seminar of the Thoracic Oncology Assembly entitled "Immunotherapy, a new standard of care in thoracic malignancies?" was held in Paris, France. This seminar provided an opportunity to review the basis of antitumour immunity and to explain how immune checkpoint inhibitors (ICIs) work. The main therapeutic trials that have resulted in marketing authorisations for use of ICIs in lung cancer were reported. A particular focus was on the toxicity of these new molecules in relation to their immune-related adverse events...
February 2018: European Respiratory Journal: Official Journal of the European Society for Clinical Respiratory Physiology
https://www.readbyqxmd.com/read/29442540/management-of-immune-related-adverse-events-in-patients-treated-with-immune-checkpoint-inhibitor-therapy-american-society-of-clinical-oncology-clinical-practice-guideline
#8
Julie R Brahmer, Christina Lacchetti, Bryan J Schneider, Michael B Atkins, Kelly J Brassil, Jeffrey M Caterino, Ian Chau, Marc S Ernstoff, Jennifer M Gardner, Pamela Ginex, Sigrun Hallmeyer, Jennifer Holter Chakrabarty, Natasha B Leighl, Jennifer S Mammen, David F McDermott, Aung Naing, Loretta J Nastoupil, Tanyanika Phillips, Laura D Porter, Igor Puzanov, Cristina A Reichner, Bianca D Santomasso, Carole Seigel, Alexander Spira, Maria E Suarez-Almazor, Yinghong Wang, Jeffrey S Weber, Jedd D Wolchok, John A Thompson
Purpose To increase awareness, outline strategies, and offer guidance on the recommended management of immune-related adverse events in patients treated with immune checkpoint inhibitor (ICPi) therapy. Methods A multidisciplinary, multi-organizational panel of experts in medical oncology, dermatology, gastroenterology, rheumatology, pulmonology, endocrinology, urology, neurology, hematology, emergency medicine, nursing, trialist, and advocacy was convened to develop the clinical practice guideline. Guideline development involved a systematic review of the literature and an informal consensus process...
February 14, 2018: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/29441454/chemotherapy-and-immunotherapy-for-recurrent-and-metastatic-head-and-neck-cancer-a-systematic-review
#9
REVIEW
Alessandro Guidi, Carla Codecà, Daris Ferrari
Head and neck cancer (HNC) is a fatal malignancy with an overall long-term survival of about 50% for all stages. The diagnosis is not rarely delayed, and the majority of patients present with loco-regionally advanced disease. The rate of second primary tumors after a diagnosis of HNC is about 3-7% per year, the highest rate among solid tumors. Currently, a single-modality or a combination of surgery, radiotherapy and chemotherapy (CHT), is the standard treatment for stage III-IV HNC. For the recurrent/metastatic setting, in the last 40 years great efforts have been made in order to develop a more effective CHT regimen, from the use of methotrexate alone, to the combination of cisplatin (CDDP) and 5-fluorouracile (5FU) or paclitaxel...
February 13, 2018: Medical Oncology
https://www.readbyqxmd.com/read/29441072/fatal-necrotizing-encephalopathy-after-treatment-with-nivolumab-for-squamous-non-small-cell-lung-cancer-case-report-and-review-of-the-literature
#10
Markus Leitinger, Mihael V Varosanec, Slaven Pikija, Romana E Wass, Dave Bandke, Serge Weis, Michael Studnicka, Susanne Grinzinger, Mark R McCoy, Larissa Hauer, Johann Sellner
Immune checkpoint inhibitors are antibodies, which enhance cellular and humoral immune responses and are approved for the treatment of various tumors. Immune-related adverse events (irAE) involving different organs and systems are, however, among the side-effects. Recent reports of severe persistent neurological deficits and even fatal cases underpin the need for better understanding of the exact pathomechanisms of central nervous system (CNS) toxicity. To our knowledge, we report the first biopsy-proven case of fatal necrotizing encephalopathy after treatment with nivolumab...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29437773/autoimmune-fasciitis-triggered-by-the-anti-programmed-cell-death-1-monoclonal-antibody-nivolumab
#11
Matthew Js Parker, Mark E Roberts, Paul C Lorigan, Daniel G du Plessis, Hector Chinoy
A 43-year-old woman with a history of recently diagnosed metastatic melanoma was commenced on systemic therapy with nivolumab, an anti-programmed cell death-1 monoclonal antibody and one of an increasing group of the so-called 'immune checkpoint inhibitors'. She experienced a dramatic complete response within 6 months of initiation. However, in addition to developing incident autoimmune hypothyroidism, she also developed progressive fatigue, proximal weakness, myalgia and dysphagia. Initial investigations with blood tests, electrophysiology and a muscle biopsy were non-specific or normal...
February 8, 2018: BMJ Case Reports
https://www.readbyqxmd.com/read/29436178/microsatellite-instability-status-determined-by-next-generation-sequencing-and-compared-with-pd-l1-and-tumor-mutational-burden-in-11-348-patients
#12
Ari Vanderwalde, David Spetzler, Nianqing Xiao, Zoran Gatalica, John Marshall
Microsatellite instability (MSI) testing identifies patients who may benefit from immune checkpoint inhibitors. We developed an MSI assay that uses data from a commercially available next-generation sequencing (NGS) panel to determine MSI status. The assay is applicable across cancer types and does not require matched samples from normal tissue. Here, we describe the MSI-NGS method and explore the relationship of MSI with tumor mutational burden (TMB) and PD-L1. MSI examined by PCR fragment analysis and NGS was compared for 2189 matched cases...
February 13, 2018: Cancer Medicine
https://www.readbyqxmd.com/read/29435437/improvement-of-antitumor-therapies-based-on-vaccines-and-immune-checkpoint-inhibitors-by-counteracting-tumor-immunostimulation
#13
Paula Chiarella, Mónica Vermeulen, Daniela R Montagna, Pablo Vallecorsa, Ariel Ramiro Strazza, Roberto P Meiss, Oscar D Bustuoabad, Raúl A Ruggiero, Richmond T Prehn
Immune-checkpoint inhibitors and antitumor vaccines may produce both tumor-inhibitory and tumor-stimulatory effects on growing tumors depending on the stage of tumor growth at which treatment is initiated. These paradoxical results are not necessarily incompatible with current tumor immunology but they might better be explained assuming the involvement of the phenomenon of tumor immunostimulation. This phenomenon was originally postulated on the basis that the immune response (IR) evoked in Winn tests by strong chemical murine tumors was not linear but biphasic, with strong IR producing inhibition and weak IR inducing stimulation of tumor growth...
2018: Frontiers in Oncology
https://www.readbyqxmd.com/read/29435193/targeted-drugs-for-systemic-therapy-of-lung-cancer-with-brain-metastases
#14
REVIEW
Ya-Wen Sun, Jian Xu, Jun Zhou, Wen-Juan Liu
Brain metastases are very common in lung cancer patients. The condition of these patients is complicated and difficult to treat, and adverse reactions following treatment can affect the nervous system, which severely reduces quality of life. Lung cancers are categorized as small cell lung cancers and non-small cell lung cancers. Patients with brain metastasis of small cell lung cancers are generally treated with brain radiotherapy and systemic chemotherapy, but stage III/IV patients with brain metastasis of non-small cell lung cancers are generally not responsive to radiotherapy or chemotherapy...
January 12, 2018: Oncotarget
https://www.readbyqxmd.com/read/29435038/high-expression-of-carcinoembryonic-antigen-and-telomerase-reverse-transcriptase-in-circulating-tumor-cells-is-associated-with-poor-clinical-response-to-the-immune-checkpoint-inhibitor-nivolumab
#15
Halin Bao, Tuya Bai, Koji Takata, Takehiko Yokobori, Takashi Ohnaga, Takeshi Hisada, Toshitaka Maeno, Pinjie Bao, Tomonori Yoshida, Yuji Kumakura, Hiroaki Honjo, Makoto Sakai, Makoto Sohda, Minoru Fukuchi, Bolag Altan, Tadashi Handa, Munenori Ide, Tatsuya Miyazaki, Kyoichi Ogata, Tetsunari Oyama, Kimihiro Shimizu, Akira Mogi, Takayuki Asao, Ken Shirabe, Hiroyuki Kuwano, Kyoichi Kaira
The present study aimed to enrich circulating tumor cells (CTCs) from blood samples using a new size-sorting CTC chip. The present study also set out to identify a blood sensitivity marker for the immune checkpoint inhibitor nivolumab in patients with advanced, pre-treatment lung cancer. The CTC sorting efficacy of the chip was investigated and the large cell fraction of blood samples from 15 patients with pre-treatment lung cancer who were later administered nivolumab were purified. The expression levels of carcinoembryonic antigen ( CEA ), human Telomerase Reverse Transcriptase ( hTERT ), cytokeratin19 ( CK19 ), and programmed death ligand-1 ( PD-L1 ) were investigated to clarify the association between these CTC markers and the clinical response to nivolumab...
March 2018: Oncology Letters
https://www.readbyqxmd.com/read/29434366/potentiating-prostate-cancer-immunotherapy-with-oncolytic-viruses
#16
REVIEW
Patrick Lee, Shashi Gujar
The clinical effectiveness of immunotherapies for prostate cancer remains subpar compared with that for other cancers. The goal of most immunotherapies is the activation of immune effectors, such as T cells and natural killer cells, as the presence of these activated mediators positively correlates with patient outcomes. Clinical evidence shows that prostate cancer is immunogenic, accessible to the immune system, and can be targeted by antitumour immune responses. However, owing to the detrimental effects of prostate-cancer-associated immunosuppression, even the newest immunotherapeutic approaches fail to initiate the clinically desired antitumour immune reaction...
February 13, 2018: Nature Reviews. Urology
https://www.readbyqxmd.com/read/29434333/improving-immunotherapy-outcomes-with-anti-angiogenic-treatments-and-vice-versa
#17
REVIEW
Kabir A Khan, Robert S Kerbel
Immunotherapies have revolutionized medical oncology following the remarkable and, in some cases, unprecedented outcomes observed in certain groups of patients with cancer. Combination with other therapeutic modalities, including anti-angiogenic agents, is one of the many strategies currently under investigation to improve the response rates and duration of immunotherapies. Such a strategy might seem counterintuitive given that anti-angiogenic agents can increase tumour hypoxia and reduce the number of blood vessels within tumours...
February 13, 2018: Nature Reviews. Clinical Oncology
https://www.readbyqxmd.com/read/29433557/metastatic-uveal-melanoma-showing-durable-response-to-anti-ctla-4-and-anti-pd-1-combination-therapy-after-experiencing-progression-on-anti-pd-1-therapy-alone
#18
Muhammad Zubair Afzal, Rodwell Mabaera, Keisuke Shirai
BACKGROUND: Uveal melanoma accounts for 85% of the ocular melanomas and has an increased risk of hematogenous spread, most commonly to the liver. After curative intent therapy like surgery and radiation, fifty percent of patients present with distant metastasis. Metastatic uveal melanoma (MUM) does not harbor typically targetable mutations, e.g., BRAF as in cutaneous melanoma. As a result, there is no proven therapy for MUM. Various chemotherapy and immunotherapy regimens have been tried and only partial response (PR) is the best that has been achieved in most of the cases...
February 12, 2018: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/29431673/a-critical-need-for-better-cancer-immunotherapy-models-are-organotypic-tumor-spheroid-cultures-the-answer
#19
Justin M Balko, Jeffrey A Sosman
Immunotherapy has transformed the therapeutic landscape of cancer, but the preclinical evaluation of combination approaches that will deepen and broaden its clinical benefit has lagged far behind due to the lack of expedient and easily accessible ex vivo human systems. In this issue, Jenkins and colleagues and Deng and colleagues report the use of organotypic cultures of tumors derived from mice and humans containing both tumor cells and cells from their local immune microenvironment to recapitulate the in vivo use of immune checkpoint inhibitors and extend the application of this system to therapeutic combinations of immune checkpoint blockade and molecularly targeted agents...
February 2018: Cancer Discovery
https://www.readbyqxmd.com/read/29429897/role-of-immunotherapy-in-bacillus-calmette-gu%C3%A3-rin-unresponsive-non-muscle-invasive-bladder-cancer
#20
REVIEW
Neelam Mukherjee, Robert S Svatek, Ahmed M Mansour
Intravesical instillation of live attenuated bacillus Calmette-Guérin (BCG) is the gold standard for patients with intermediate- and high-risk non-muscle-invasive bladder cancer (NMIBC). BCG-failures include a heterogenous population of patients who share a designation of disease recurrence or progression following BCG and include patients with complete unresponsiveness to BCG, patients who respond initially but develop relapse and, in some cases, patients who are intolerant to BCG due to side effects. Given the efficacy and relatively rapid approval of several monoclonal antibodies against PD-L1 or PD-1 for advanced and metastatic bladder cancer, the role of these checkpoint inhibitors in BCG-relapsing disease at various disease stages is under consideration...
February 8, 2018: Urologic Oncology
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