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Immunotherapy In Lung Cancer

Rodolfo Servín-Blanco, Rosa Mariana Chávaro-Ortiz, Rubén Zamora-Alvarado, Fernando Martínez-Cortes, Goar Gevorkian, Karen Manoutcharian
Although various immune checkpoint inhibitors (ICIs), used for the treatment of advanced cancer, showed remarkably durable tumor regression in a subset of patients, there are important limitations in a large group of non-responders, and the generation of novel immunogens capable of inducing protective cellular immune responses is a priority in cancer immunotherapy field. During the last decades, several types of vaccine immunogens have been used in numerous preclinical studies and clinical trials. However, although immunity to tumor Ags can be elicited by most vaccines tested, their clinical efficacy remains modest...
October 16, 2018: Immunology Letters
Sadakatsu Ikeda, Sheryl K Elkin, Brett N Tomson, Jennifer L Carter, Razelle Kurzrock
Despite being one of the most common cancers, treatment options for prostate cancer are limited. Novel approaches for advanced disease are needed. We evaluated the relative rate of use of clinical-grade next generation sequencing (NGS) in prostate cancer, as well as genomic alterations identified and their potential actionability. Of 4864 patients from multiple institutions for whom NGS was ordered by physicians, only 67 (1.4%) had prostate cancer, representing 1/10 the ordering rate for lung cancer. Prostate cancers harbored 148 unique alterations affecting 63 distinct genes...
October 19, 2018: Cancer Biology & Therapy
A Lupo, M Alifano, M Wislez, G Boulle, Y Velut, J Biton, I Cremer, F Goldwasser, K Leroy, D Damotte
Immune checkpoint inhibitors (ICI), targeting the PD1/PD-L1 axis has shown their efficacy in lung cancer but only in a restricted population of patients, thus it is mandatory to identify biomarkers predicting the clinical benefit. In this article we will describe and analyzed biomarkers already published, from protein, to RNA and at last DNA markers, discussing each markers feasibility and interest. In the future, combined analysis of several markers will probably be proposed, particularly with the increasing complexity of therapy schema with molecules association...
October 15, 2018: Revue de Pneumologie Clinique
Dina M El-Guindy, Duaa S Helal, Nesreen M Sabry, Mohamed Abo El-Nasr
Cancer immunotherapy targeting programmed cell death-1/programmed cell death ligand-1 (PD-1/PD-L1) pathway has shown promising results in treatment of non-small cell lung cancer (NSCLC) patients. T cells play a major role in tumor-associated immune response. This study aimed to investigate PD-L1 expression alone and combined with CD8 tumor infiltrating lymphocytes (TILs) density in relation to clinicopathologic parameters and survival in NSCLC patients. Immunohistochemical analysis was used to evaluate PD-L1 expression and CD8 TILs density in 55 NSCLC patients...
October 15, 2018: Journal of the Egyptian National Cancer Institute
Kazuhisa Tanaka, Yuri Kanesaka, Mariko Takami, Akane Suzuki, Hiroyuki Hosokawa, Atsushi Onodera, Toshiko Kamata, Kaoru Nagato, Toshinori Nakayama, Ichiro Yoshino, Shinichiro Motohashi
Invariant natural killer T (iNKT) cells exhibit potent antitumor effects upon activation by recognizing a specific glycolipid antigen. We previously performed phase I-II clinical studies to utilize iNKT cells using α-galactosylceramide-pulsed dendritic cells and identified leukotriene B4 12-hydroxydehydrogenase (LTB4DH) as a biomarker highly expressed in T cells derived from non-small cell lung cancer (NSCLC) patients who showed prolonged survival in respond to the iNKT cell immunotherapy. Because LTB4DH expression correlated with prolonged survival of NSCLC patients, we considered LTB4DH to play a role in iNKT cell immunotherapy...
October 15, 2018: Biochemical and Biophysical Research Communications
M Oellerich, E Schütz, J Beck, P D Walson
Genomic analyses in oncologic care allow for the development of more precise clinical laboratory tests that will be critical for personalized pharmacotherapy. Traditional biopsy-based approaches are limited by the availability of sequential tissue specimens to detect resistance. Blood-based genomic profiling ("liquid biopsy") is useful for longitudinal monitoring of tumor genomes and can complement biopsies. Tumor-associated mutations can be identified in cell-free tumor DNA (ctDNA) from patient blood samples and used for monitoring disease activity...
October 16, 2018: Therapeutic Drug Monitoring
Masaki Kanazu, Ryuya Edahiro, Hiroyuki Krebe, Kohei Nishida, Mikako Ishijima, Takeshi Uenami, Yuki Akazawa, Yukihiro Yano, Toshihiko Yamaguchi, Masahide Mori
Nivolumab is an anti-PD-1 blocking monoclonal antibody approved for the treatment of non-small cell lung cancer (NSCLC). However, some patients on immunotherapy may experience rapid progression and worsening clinical status, known as hyperprogressive disease. We retrospectively reviewed the clinical records of patients with NSCLC administered nivolumab therapy at Toneyama National Hospital, Japan, from January 2016 to January 2018. Of the 87 patients administered nivolumab therapy, five experienced rapid progression during one cycle of nivolumab therapy...
October 17, 2018: Thoracic Cancer
Katrien Ghysen, Johan Vansteenkiste
PURPOSE OF REVIEW: 'Early-stage' nonsmall cell lung cancer (NSCLC) refers to stage I and stage II disease, and selected cases of stage IIIA disease where complete tumor resection is feasible. Surgery is the standard treatment for early NSCLC, but the overall 5-year survival remains below 50%. The addition of adjuvant cisplatin-based chemotherapy to surgery improved 5-year survival rates by 5-10%, but no significant therapeutic innovation has been established thereafter. We review recent and ongoing studies looking how immunotherapy may improve the outcome of these patients...
October 15, 2018: Current Opinion in Oncology
Massimiliano Salati, Cinzia Baldessari, Fiorella Calabrese, Giulio Rossi, Elisa Pettorelli, Giulia Grizzi, Massimo Dominici, Fausto Barbieri
Background: Pulmonary sarcomatoid carcinoma is a rare, poorly differentiated, and highly aggressive type of non-small cell lung cancer. High tumor mutational burden and PD-L1 overexpression make it an excellent candidate for immunotherapy. Objectives and Method: We presented the case of a patient who underwent left inferior lobectomy with concurrent right paravertebral muscular metastasectomy for an infiltrative neoplastic mass, whose final diagnosis was consistent with stage IV pulmonary sarcomatoid carcinoma...
September 2018: Case Reports in Oncology
Barbara Rath, Maximilian Hochmair, Adelina Plangger, Gerhard Hamilton
Lung cancer is a leading cause of tumor-associated mortality. Fascaplysin, a bis-indole of a marine sponge, exhibit broad anticancer activity as specific CDK4 inhibitor among several other mechanisms, and is investigated as a drug to overcome chemoresistance after the failure of targeted agents or immunotherapy. The cytotoxic activity of fascaplysin was studied using lung cancer cell lines, primary Non-Small Cell Lung Cancer (NSCLC) and Small Cell Lung Cancer (SCLC) cells, as well as SCLC circulating tumor cell lines (CTCs)...
October 14, 2018: Marine Drugs
Suneel D Kamath, Priya U Kumthekar
While the CNS has long been viewed as an immune-privileged environment, a paradigm shift in neuro-immunology has elevated the role of systemic immunotherapy for the treatment of metastatic disease. Increasing knowledge regarding the presence of a CNS lymphatic system and the physical and biochemical alteration of the blood brain barrier (BBB) by the tumor microenvironment suggests immune cell trafficking in and out of the CNS is possible. Emerging clinical data suggest immune checkpoint inhibitors (ICIs) can stimulate T cells peripherally to in turn have anti-tumor effects in the CNS...
2018: Frontiers in Oncology
Jean-David Fumet, Corentin Richard, Fanny Ledys, Quentin Klopfenstein, Philippe Joubert, Bertrand Routy, Caroline Truntzer, Andréanne Gagné, Marc-André Hamel, Camila Figueiredo Guimaraes, Bruno Coudert, Laurent Arnould, Laure Favier, Aurélie Lagrange, Sylvain Ladoire, Pierre Saintigny, Sandra Ortiz-Cuaran, Maurice Perol, Pascal Foucher, Paul Hofman, Marius Ilie, Sandy Chevrier, Romain Boidot, Valentin Derangere, François Ghiringhelli
BACKGROUND: No study has evaluated the predictive and prognostic role of CD8 and PD-L1 coexpression in non-small-cell lung cancer (NSCLC). METHODS: We analyzed RNA sequencing and/or immunohistochemistry staining in NSCLC patients from The Cancer Genome Atlas (n = 1016), and 34 metastatic NSCLC samples not treated by immunotherapy as prognostic cohorts. As predictive aspect of CD8 and PD-L1, we used 85 NSCLC patients treated with anti-PD-1. Two validation cohorts were used including 44 NSCLC patients treated with anti-PD-1 and an external cohort with different tumor types...
October 15, 2018: British Journal of Cancer
G Eberst, W Lakhzoum, P Tomasini, N Andreotti, J Abcaya, C Mascaux, F Barlesi
INTRODUCTION: Specific immune-related adverse events in lung cancer treatment are rare and it is important that they are identified as they may have important adverse consequences. We report such a case here. CASE REPORT: A Caucasian female diagnosed with KRAS mutant advanced adenocarcinoma of the lung was enrolled in a phase Ib trial assessing the combination of an anti cytotoxic T-lymphocyte- associated protein 4 antibody and a programmed death-Ligand 1 inhibitor...
October 11, 2018: Revue des Maladies Respiratoires
V Brie, M Faure, J Garon, I Petit, E Gomez, A Knoepfli, M Decavele, N Petitpain, F Chabot, A Chaouat
INTRODUCTION: The anti programmed death-1 (PD-1) and the programmed death ligand 1 (PD-L1) antibodies are used as immunotherapies in the treatment of many solid tumours. Cases of interstitial pneumonitis induced by anti PD-1 have been widely described, but there are fewer data with anti PD-L1. Avelumab is a new immunotherapy of the anti PD-L1 class. CASE REPORT: A 66-year-old woman, ex-smoker, had been treated with avelumab and axitinib since November 2016 for renal cell cancer...
October 11, 2018: Revue des Maladies Respiratoires
Lizet Sanchez, Leacky Muchene, Patricia Lorenzo-Luaces, Carmen Viada, Pedro C Rodriguez, Sailyn Alfonso, Tania Crombet, Elia Neninger, Ziv Shkedy, Agustin Lage
BACKGROUND: Progress in immunotherapy has revolutionized the treatment landscape for advanced lung cancer, with emerging evidence of patients experiencing long-term survivals. The goal of this study was to explore the existence of short- and long-term survival populations and to assess the effect of immunotherapy on them. METHODS: Data from two randomized, multicenter, controlled clinical trials was used to evaluate the effect of two therapeutic vaccines (anti-idiotypic vaccine VAXIRA and anti-EGF vaccine CIMAVAX) on survival curves in advanced non-small cell lung cancer patients...
January 2018: Seminars in Oncology
Hong Zhang, Shimin Pei, Bin Zhou, Huanan Wang, Hongchao Du, Di Zhang, Degui Lin
Canine mammary tumor (CMT) has always been an ideal animal model for human breast cancer (HBC) research, however, there is a lack of various established CMT cell lines corresponding to HBC cell lines. This study was designed to establish a new type of CMT cell line. The primary tumor, CMT-7364, was identified as the intraductal papillary carcinoma, and showed negative immunoreactivity to estrogen receptors (ER), progesterone receptors (PR), and human epidermal growth factor receptor-2 (HER-2) by immunohistochemistry (IHC) analysis...
October 2018: Tissue & Cell
Julie Garon-Czmil, Nadine Petitpain, Franck Rouby, Marion Sassier, Samy Babai, Mélissa Yelehe-Okouma, Georges Weryha, Marc Klein, Pierre Gillet
Immunotherapy with immune checkpoint inhibitors (ICIs) for cancer has become increasingly prescribed in recent years. Indeed, it is used to treat both solid and hematological malignancies due to their considerable potential in treating melanoma, non-small cell lung and other cancers. Immune-mediated related adverse endocrine toxicity, and especially thyroiditis, are seen as a growing problem needing specific screening and management. This study aims at describing thyroid dysfunctions induced by the ICIs marketed in France, which are registered in the French Pharmacovigilance database...
October 11, 2018: Fundamental & Clinical Pharmacology
Giovanni Fucà, Giulia Galli, Marta Poggi, Giuseppe Lo Russo, Claudia Proto, Martina Imbimbo, Milena Vitali, Monica Ganzinelli, Claudia Lanti, Giuliano Molino, Fabiano Stangoni, Nicoletta Zilembo, Filippo de Braud, Marina Chiara Garassino, Diego Signorelli
BACKGROUND: A consistent percentage of patients with metastatic non-small cell lung cancer (NSCLC) derives no or only marginal benefit from immunotherapy (IO). OBJECTIVE: Since serum sodium has been linked to both prognosis in NSCLC and modulation of immune cells activity, we aimed to assess the association between low baseline serum sodium concentration (≤ 135 mEq/L) and clinical outcomes of patients with metastatic NSCLC treated with IO. PATIENTS AND METHODS: We included metastatic NSCLC patients treated with checkpoint inhibitors in our department from April 2013 to April 2018 with available baseline serum sodium concentration...
October 10, 2018: Targeted Oncology
Jan Norum, Carsten Nieder
Background: Programmed death ligand 1 (PD-L1) targeting immunotherapies, as pembrolizumab and nivolumab, have significantly improved outcome in patients with non-small cell lung cancer (NSCLC). Tobacco smoking is the number one risk factor for lung cancer and is linked to 80%-90% of these cancers. Smoking during cancer therapy may influence on radiotherapy and chemotherapy outcome. We aimed to review the knowledge in immunotherapy. Patients and methods: A systematic review was done...
2018: ESMO Open
Kendall F Moseley, Jarushka Naidoo, Clifton O Bingham, Michael A Carducci, Patrick M Forde, Geoffrey T Gibney, Evan J Lipson, Ami A Shah, William H Sharfman, Laura C Cappelli
BACKGROUND: The use of immune checkpoint inhibitors is increasing in cancer therapy today. It is critical that treatment teams become familiar with the organ systems potentially impacted by immune-related adverse events associated with these drugs. Here, we report adverse skeletal effects of immunotherapy, a phenomenon not previously described. CASE PRESENTATIONS: In this retrospective case series, clinical, laboratory and imaging data were obtained in patients referred to endocrinology or rheumatology with new fractures (n = 3) or resorptive bone lesions (n = 3) that developed while on agents targeting PD-1, CTLA-4 or both...
October 11, 2018: Journal for Immunotherapy of Cancer
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