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Immunotherapy In Lung Cancer

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https://www.readbyqxmd.com/read/30109465/anti-gaba-b-receptor-encephalitis-in-a-patient-with-gastric-adenocarcinoma
#1
Xiao-Tao Jia, Yanfang Pan, Zhengli Di, Naibing Gu, Zhiqin Liu, Yu-Ming Kang
Anti-γ-aminobutyric acid-B (GABAB ) receptor encephalitis is an autoimmune encephalitis associated with antibodies against neuronal cell surface antigens, which are primarily observed with small-cell lung cancer, melanoma, and thymoma. Here, we first report a case on the association between a relatively frequent cancer, gastric adenocarcinoma (GAC), and a rare GABAB receptor antibody limbic encephalitis. The patient was treated with immunotherapy and combined-drug chemotherapy, which were partially effective in terms of stabilizing the tumor and relieving neurological symptoms...
August 14, 2018: Neurological Sciences
https://www.readbyqxmd.com/read/30105645/the-role-of-targeted-agents-and-immunotherapy-in-older-patients-with-non-small-cell-lung-cancer
#2
REVIEW
Fabio Gomes, Rebecca Tay, Jaseela Chiramel, Raffaele Califano
Lung cancer is predominantly a disease of the elderly. This subgroup of patients poses many challenges and an appropriate geriatric assessment is crucial for treatment personalisation in order to reduce the risk of over- or under-treatment. Whilst cytotoxic chemotherapy has been the backbone of advanced non-small cell lung cancer (NSCLC) treatment for decades, the development of targeted agents for driver mutations such as EGFR, ALK, BRAF and ROS1 has changed the treatment paradigm and natural history of this disease...
August 14, 2018: Drugs & Aging
https://www.readbyqxmd.com/read/30105218/review-of-checkpoint-immunotherapy-for-the-management-of-non-small-cell-lung-cancer
#3
REVIEW
Shine Raju, Ranjit Joseph, Sameep Sehgal
Checkpoint immunotherapy uses highly selective humanized monoclonal antibodies against checkpoint signals such as programmed cell death receptor (PD-1) and programmed cell death ligand (PD-L1). By blocking these receptors and signals, the immune system can be reactivated to fight the tumor. Immunotherapy for advanced non-small cell lung cancer (NSCLC) has resulted in a new paradigm of treatment options resulting in improved survival and response rates and has a less severe yet unique toxicity profile when compared to chemotherapy...
2018: ImmunoTargets and Therapy
https://www.readbyqxmd.com/read/30105035/cancer-cell-intrinsic-pd-1-and-implications-in-combinatorial-immunotherapy
#4
REVIEW
Han Yao, Huanbin Wang, Chushu Li, Jing-Yuan Fang, Jie Xu
Programmed death 1 (PD-1) and its two natural ligands PD-L1 and PD-L2 are responsible for delivering inhibitory signals that regulate the balance between T cell activation, tolerance, and immunopathology. In previous studies, PD-1 was found only expressed on the surface of immune cells, such as T cells and B cells while PD-1's ligands PD-L1 and PD-L2 were found expressed in some tumor cells. However, recent studies revealed intrinsic expression of PD-1 in melanoma and some other cancers. In melanoma cells, PD-1 can be activated by its ligand PD-L1 expressed by tumor cells, modulating downstream mammalian target of rapamycin signaling and promoting tumor growth independent of adaptive immunity...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/30104155/the-efficacy-and-toxicity-of-immune-checkpoint-inhibitors-in-a-real-world-older-patient-population
#5
Joobin Sattar, Adi Kartolo, Wilma M Hopman, Joshua Matthew Lakoff, Tara Baetz
IMPORTANCE: Immunotherapy has emerged as an effective treatment option for the management of advanced cancers. The effects of these immune checkpoint inhibitors in the older patient population has not been adequately assessed. OBJECTIVE: To understand the impact of aging on CTLA-4 and PDL-1 inhibitors efficacy and immune-related adverse events (irAE) in the context of real-world management of advanced solid cancers. DESIGN, SETTING, AND PARTICIPANTS: This retrospective study involved all non-study patients with histologically-confirmed metastatic or inoperable solid cancers receiving immunotherapy at Kingston Health Sciences Centre...
August 10, 2018: Journal of Geriatric Oncology
https://www.readbyqxmd.com/read/30104030/current-uses-of-check-inhibitors-in-the-fight-against-advanced-and-or-metastatic-lung-cancer-will-immunotherapy-overcome-chemotherapy
#6
REVIEW
Bulent Cetin, İrem Bilgetekin, Ahmet Ozet
Lung cancer is the most common cause of cancer death worldwide. Treatment for lung cancer has become increasingly more complex over the last several years. Immune checkpoint inhibitors have dramatically changed the treatment landscape of advanced nonsmall cell lung cancer (NSCLC). There are currently 3 approved checkpoint inhibitors for patients with NSCLC who progressed after platinum-doublet chemotherapy (Pembrolizumab and /or Nivolumab and /or Atezolizumab). Avelumab and durvalumab are currently under investigation in phase 3 trials...
August 4, 2018: Current Problems in Cancer
https://www.readbyqxmd.com/read/30101407/invasive-pulmonary-aspergillosis-complicated-by-carbapenem-resistant-pseudomonas-aeruginosa-infection-during-pembrolizumab-immunotherapy-for-metastatic-lung-adenocarcinoma-case-report-and-review-of-the-literature
#7
Chiara Oltolini, Marco Ripa, Andrea Andolina, Elena Brioschi, Marta Cilla, Giovanna Petrella, Vanesa Gregorc, Barbara Castiglioni, Chiara Tassan Din, Paolo Scarpellini
The widespread use of T lymphocyte-associated antigen-4 (CTLA-4) and programmed death (PD)-1 and PD ligand-1 (PDL1)-targeted agents in cancer patients as immunotherapy has raised some issues on their safety profile. Regarding infectious complications, it has emerged that these compounds do not intrinsically increase susceptibility to opportunistic infections, which mainly correlate with the co-administration of systemic immunosuppressive therapy (high-dose corticosteroids and anti-tumor necrosis factors inhibitors) to cure immune-related adverse events (colitis, hepatitis, pneumonitis and pancreatitis), well-known complications of these targeted drugs...
August 13, 2018: Mycopathologia
https://www.readbyqxmd.com/read/30100403/epigenetic-prediction-of-response-to-anti-pd-1-treatment-in-non-small-cell-lung-cancer-a-multicentre-retrospective-analysis
#8
Michäel Duruisseaux, Anna Martínez-Cardús, Maria E Calleja-Cervantes, Sebastian Moran, Manuel Castro de Moura, Veronica Davalos, David Piñeyro, Montse Sanchez-Cespedes, Nicolas Girard, Marie Brevet, Etienne Giroux-Leprieur, Coraline Dumenil, Monica Pradotto, Paolo Bironzo, Enrica Capelletto, Silvia Novello, Alexis Cortot, Marie-Christine Copin, Niki Karachaliou, Maria Gonzalez-Cao, Sergio Peralta, Luis M Montuenga, Ignacio Gil-Bazo, Iosune Baraibar, Maria D Lozano, Mar Varela, Jose C Ruffinelli, Ramon Palmero, Ernest Nadal, Teresa Moran, Lidia Perez, Immaculada Ramos, Qingyang Xiao, Agustin F Fernandez, Mario F Fraga, Marta Gut, Ivo Gut, Cristina Teixidó, Noelia Vilariño, Aleix Prat, Noemi Reguart, Amparo Benito, Pilar Garrido, Isabel Barragan, Jean-François Emile, Rafael Rosell, Elisabeth Brambilla, Manel Esteller
BACKGROUND: Anti-programmed death-1 (PD-1) treatment for advanced non-small-cell lung cancer (NSCLC) has improved the survival of patients. However, a substantial percentage of patients do not respond to this treatment. We examined the use of DNA methylation profiles to determine the efficacy of anti-PD-1 treatment in patients recruited with current stage IV NSCLC. METHODS: In this multicentre study, we recruited adult patients from 15 hospitals in France, Spain, and Italy who had histologically proven stage IV NSCLC and had been exposed to PD-1 blockade during the course of the disease...
August 9, 2018: Lancet Respiratory Medicine
https://www.readbyqxmd.com/read/30100188/generation-of-tumor-reactive-t-cells-by-co-culture-of-peripheral-blood-lymphocytes-and-tumor-organoids
#9
Krijn K Dijkstra, Chiara M Cattaneo, Fleur Weeber, Myriam Chalabi, Joris van de Haar, Lorenzo F Fanchi, Maarten Slagter, Daphne L van der Velden, Sovann Kaing, Sander Kelderman, Nienke van Rooij, Monique E van Leerdam, Annekatrien Depla, Egbert F Smit, Koen J Hartemink, Rosa de Groot, Monika C Wolkers, Norman Sachs, Petur Snaebjornsson, Kim Monkhorst, John Haanen, Hans Clevers, Ton N Schumacher, Emile E Voest
Cancer immunotherapies have shown substantial clinical activity for a subset of patients with epithelial cancers. Still, technological platforms to study cancer T-cell interactions for individual patients and understand determinants of responsiveness are presently lacking. Here, we establish and validate a platform to induce and analyze tumor-specific T cell responses to epithelial cancers in a personalized manner. We demonstrate that co-cultures of autologous tumor organoids and peripheral blood lymphocytes can be used to enrich tumor-reactive T cells from peripheral blood of patients with mismatch repair-deficient colorectal cancer and non-small-cell lung cancer...
August 3, 2018: Cell
https://www.readbyqxmd.com/read/30099376/evolving-paradigms-in-hiv-malignancies-review-of-ongoing-clinical-trials
#10
REVIEW
Rachel Bender Ignacio, Lilie L Lin, Lakshmi Rajdev, Elizabeth Chiao
This review highlights current interventional clinical trials for HIV-associated malignancies (HIVAMs), with emphasis on 4 mechanistic areas: immunomodulatory therapies and gene therapies, including immune checkpoint inhibitors; cytotoxic therapies; novel tumor-targeted and virally targeted therapies in both AIDS-defining and non-AIDS-defining cancers (NADC); and other screening or topical/ablative interventions. A search on ClinicalTrials.gov located 35 trials, including 12 immunomodulatory or gene therapy trials, 6 cytotoxic therapy trials, 10 trials of therapies with tumor or viral molecular targets, and 7 trials evaluating screening interventions or topical or ablative therapies...
August 2018: Journal of the National Comprehensive Cancer Network: JNCCN
https://www.readbyqxmd.com/read/30095976/immune-checkpoint-ligand-pd-l1-is-upregulated-in-pulmonary-lymphangioleiomyomatosis-lam
#11
Katharina Maisel, Mervyn J Merrilees, Elena N Atochina-Vasserman, Lurong Lian, Kseniya Obraztsova, Ryan Rue, Alexander N Vasserman, Ning Zuo, Luis F Angel, Andrew J Gow, Inkyung Kang, Thomas N Wight, Evgeniy Eruslanov, Melody A Swartz, Vera P Krymskaya
Pulmonary Iymphangioleiomyomatosis (LAM) is a slow-progressing metastatic disease that is driven by mutations in the tumor suppressor tuberous sclerosis complex 1/2 (TSC1/2). Rapamycin inhibits LAM cell proliferation and is the only approved treatment, yet it can only stabilize the disease but not cause regression of existing lesions. However, in other cancers, immunotherapies such as checkpoint blockade against PD-1 and its ligand PD-L1 have shown promise in causing tumor regression and even curing some patients...
August 10, 2018: American Journal of Respiratory Cell and Molecular Biology
https://www.readbyqxmd.com/read/30094067/csf-1-and-ang-2-serum-levels-prognostic-and-diagnostic-partners-in-non-small-cell-lung-cancer
#12
Ana Luísa Coelho, Mónica Patrícia Gomes, Raquel Jorge Catarino, Christian Rolfo, Rui Manuel Medeiros, António Manuel Araújo
Background: Lung cancer is the most incident and lethal form of cancer, with late diagnosis as a major determinant of its bad prognosis. Immunotherapies targeting immune checkpoints improve survival, but positive results encompass only 30%-40% of the patients, possibly due to alternative pathways to immunosuppression, including tumour-associated macrophages (TAM). Colony stimulating factor-1 (CSF-1) is implicated in TAM differentiation and recruitment to tumours and in tumour angiogenesis, through a special setting of Tie-2-expressing macrophages, which respond to angiopoietin-2 (Ang-2)...
2018: ESMO Open
https://www.readbyqxmd.com/read/30094028/pembrolizumab-induced-myasthenia-gravis-with-myositis-in-a-patient-with-lung-cancer
#13
Makoto Hibino, Kazunari Maeda, Shigeto Horiuchi, Minoru Fukuda, Tetsuri Kondo
In the new era of cancer immunotherapy, clinical research has uncovered diverse and unpredictable immune-related adverse events. Here, we report the first case of pembrolizumab-induced myasthenia gravis (MG) and myositis in a patient with lung cancer. The patient developed symptoms after the second infusion of pembrolizumab and was successfully treated with systemic corticosteroid therapy. With the accelerated development of immune checkpoint inhibitors as mono- or combination therapies for various malignancies, clinicians should closely monitor patients for important immune-related adverse events, such as MG, especially during the early phase of the treatment...
October 2018: Respirology Case Reports
https://www.readbyqxmd.com/read/30093454/early-reduction-in-ctdna-predicts-survival-in-lung-and-bladder-cancer-patients-treated-with-durvalumab
#14
Rajiv Raja, Michael Kuziora, Philip Brohawn, Brandon W Higgs, Ashok Gupta, Phillip A Dennis, Koustubh Ranade
PURPOSE: Immunotherapy has transformed the treatment of many solid tumors, with some patients deriving long-term benefit, but how to identify such patients remains unclear. Somatic mutations detected in circulating tumor DNA (ctDNA) from plasma can be an indicator of disease progression, response to therapy and clonality of primary and metastatic lesions. Hence, ctDNA analysis can provide a valuable noninvasive and tumor-specific marker for longitudinal monitoring of tumor burden. We explored the use of ctDNA to predict survival on durvalumab, an anti-PD-L1 therapy...
August 9, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/30089601/case-control-study-of-pd-1-pd-l1-and-b7-h3-expression-in-lung-cancer-patients-with-and-without-human-immunodeficiency-virus-hiv-infection
#15
Katherine A Scilla, Dan P Zandberg, Søren M Bentzen, Candace Mainor, Jonathon Heath, Olga B Ioffe, Ashley L Cellini, Martin J Edelman, David J Riedel, Josephine L Feliciano
OBJECTIVE: Co-signaling molecules PD-L1, B7-H3, and PD-1 play a key role in cancer immunology. There are limited but emerging data on expression of these molecules in HIV-infected lung cancer patients. MATERIALS AND METHODS: We reviewed archived lung cancer tissue samples from HIV-infected cases (n = 13) and HIV-uninfected controls (n = 13) from 2001-2015. Cases and controls were matched by histology and stage. Immunostained tumor sections were analyzed for percent of tumor cells expressing PD-L1 and B7-H3, and percent of tumor infiltrating immune cells (TII) expressing PD-1 and PD-L1...
September 2018: Lung Cancer: Journal of the International Association for the Study of Lung Cancer
https://www.readbyqxmd.com/read/30082906/management-guidelines-for-paediatric-patients-receiving-chimeric-antigen-receptor-t-cell-therapy
#16
REVIEW
Kris M Mahadeo, Sajad J Khazal, Hisham Abdel-Azim, Julie C Fitzgerald, Agne Taraseviciute, Catherine M Bollard, Priti Tewari, Christine Duncan, Chani Traube, David McCall, Marie E Steiner, Ira M Cheifetz, Leslie E Lehmann, Rodrigo Mejia, John M Slopis, Rajinder Bajwa, Partow Kebriaei, Paul L Martin, Jerelyn Moffet, Jennifer McArthur, Demetrios Petropoulos, Joan O'Hanlon Curry, Sarah Featherston, Jessica Foglesong, Basirat Shoberu, Alison Gulbis, Maria E Mireles, Lisa Hafemeister, Cathy Nguyen, Neena Kapoor, Katayoun Rezvani, Sattva S Neelapu, Elizabeth J Shpall
In 2017, an autologous chimeric antigen receptor (CAR) T cell therapy indicated for children and young adults with relapsed and/or refractory CD19+ acute lymphoblastic leukaemia became the first gene therapy to be approved in the USA. This innovative form of cellular immunotherapy has been associated with remarkable response rates but is also associated with unique and often severe toxicities, which can lead to rapid cardiorespiratory and/or neurological deterioration. Multidisciplinary medical vigilance and the requisite health-care infrastructure are imperative to ensuring optimal patient outcomes, especially as these therapies transition from research protocols to standard care...
August 6, 2018: Nature Reviews. Clinical Oncology
https://www.readbyqxmd.com/read/30082870/blood-based-tumor-mutational-burden-as-a-predictor-of-clinical-benefit-in-non-small-cell-lung-cancer-patients-treated-with-atezolizumab
#17
David R Gandara, Sarah M Paul, Marcin Kowanetz, Erica Schleifman, Wei Zou, Yan Li, Achim Rittmeyer, Louis Fehrenbacher, Geoff Otto, Christine Malboeuf, Daniel S Lieber, Doron Lipson, Jacob Silterra, Lukas Amler, Todd Riehl, Craig A Cummings, Priti S Hegde, Alan Sandler, Marcus Ballinger, David Fabrizio, Tony Mok, David S Shames
Although programmed death-ligand 1-programmed death 1 (PD-L1-PD-1) inhibitors are broadly efficacious, improved outcomes have been observed in patients with high PD-L1 expression or high tumor mutational burden (TMB). PD-L1 testing is required for checkpoint inhibitor monotherapy in front-line non-small-cell lung cancer (NSCLC). However, obtaining adequate tumor tissue for molecular testing in patients with advanced disease can be challenging. Thus, an unmet medical need exists for diagnostic approaches that do not require tissue to identify patients who may benefit from immunotherapy...
August 6, 2018: Nature Medicine
https://www.readbyqxmd.com/read/30081936/can-ido-activity-predict-primary-resistance-to-anti-pd-1-treatment-in-nsclc
#18
Andrea Botticelli, Bruna Cerbelli, Luana Lionetto, Ilaria Zizzari, Massimiliano Salati, Annalinda Pisano, Mazzuca Federica, Maurizio Simmaco, Marianna Nuti, Paolo Marchetti
BACKGROUND: Immune checkpoint inhibitors have revolutionized the treatment paradigm of highly lethal malignancies like advanced non-small cell lung cancer (NSCLC), demonstrating long-term tumour control and extended patient survival. Unfortunately, only 25-30% of patients experience a durable benefit, while the vast majority demonstrate primary or acquired resistance. Recently, indoleamine 2,3-dioxygenase (IDO) activity has been proposed as a possible mechanism of resistance to anti-PD-1 treatment leading to an immunosuppressive microenvironment...
August 6, 2018: Journal of Translational Medicine
https://www.readbyqxmd.com/read/30080893/a-fully-virulent-retargeted-oncolytic-hsv-armed-with-il-12-elicits-local-immunity-and-vaccine-therapy-towards-distant-tumors
#19
Valerio Leoni, Andrea Vannini, Valentina Gatta, Julie Rambaldi, Mara Sanapo, Catia Barboni, Anna Zaghini, Patrizia Nanni, Pier-Luigi Lollini, Costanza Casiraghi, Gabriella Campadelli-Fiume
Oncolytic herpes simplex viruses (oHSVs) showed efficacy in clinical trials and practice. Most of them gain cancer-specificity from deletions/mutations in genes that counteract the host response, and grow selectively in cancer cells defective in anti-viral response. Because of the deletions/mutations, they are frequently attenuated or over-attenuated. We developed next-generation oHSVs, which carry no deletion/mutation, gain cancer-specificity from specific retargeting to tumor cell receptors-e.g. HER2 (human epidermal growth factor receptor 2)-hence are fully-virulent in the targeted cancer cells...
August 6, 2018: PLoS Pathogens
https://www.readbyqxmd.com/read/30077124/the-role-of-immune-microenvironment-in-small-cell-lung-cancer-distribution-of-pd-l1-expression-and-prognostic-role-of-foxp3-positive-tumour-infiltrating-lymphocytes
#20
L Bonanno, A Pavan, M V Dieci, E Di Liso, M Schiavon, G Comacchio, I Attili, G Pasello, F Calabrese, F Rea, A Favaretto, M Rugge, V Guarneri, M Fassan, P F Conte
INTRODUCTION: The prognosis of small-cell lung cancer (SCLC) is dismal and new effective therapies are needed. Immunotherapy looks promising, but no molecular predictive markers are currently available, and data on immune microenvironment are very limited. METHODS: We retrospectively analysed 104 SCLC cases. Immunohistochemistry evaluation of PD-L1 was performed both on tumour cells (TCs) and on tumour-infiltrating immune cells (TIICs) by using anti-PD-L1 22C3 antibody (DAKO) and categorised by using 1% as cut-off point...
August 1, 2018: European Journal of Cancer
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