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Immunotherapy In Lung Cancer

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https://read.qxmd.com/read/30885550/correlations-between-the-immune-related-adverse-events-spectrum-and-efficacy-of-anti-pd1-immunotherapy-in-nsclc-patients
#1
Alessio Cortellini, Rita Chiari, Biagio Ricciuti, Giulio Metro, Fabiana Perrone, Marcello Tiseo, Melissa Bersanelli, Paola Bordi, Daniele Santini, Raffaele Giusti, Antonino Grassadonia, Pietro Di Marino, Nicola Tinari, Michele De Tursi, Federica Zoratto, Enzo Veltri, Francesco Malorgio, Carlo Garufi, Marco Russano, Cecilia Anesi, Tea Zeppola, Marco Filetti, Paolo Marchetti, Rossana Berardi, Silvia Rinaldi, Marianna Tudini, Rosa Rita Silva, Annagrazia Pireddu, Francesco Atzori, Daniela Iacono, Maria Rita Migliorino, Giampiero Porzio, Katia Cannita, Corrado Ficorella, Sebastiano Buti
BACKGROUND: Immune-related adverse events (irAEs) developed during immunotherapy with anti-PD-1 agents, could be a predictive surrogate marker of clinical benefit in patients with advanced non-small-cell lung cancer (NSCLC). METHODS: Patients with NSCLC, treated with anti-PD-1 agents, were retrospectively evaluated. Univariate and multivariate analyses were performed to evaluate the relationships between types of irAEs (differentiated according to system/organ involved and to single-site/multiple-site), overall response rate (ORR), progression-free survival (PFS) and overall survival (OS)...
February 21, 2019: Clinical Lung Cancer
https://read.qxmd.com/read/30885360/pathways-and-epigenetic-based-assessment-of-relative-immune-infiltration-in-various-types-of-solid-tumors
#2
Manny D Bacolod, Francis Barany, Karsten Pilones, Paul B Fisher, Romulo J de Castro
Recent clinical studies document the power of immunotherapy in treating subsets of patients with advanced cancers. In this context and with multiple cancer immunotherapeutics already evaluated in the clinic and a large number in various stages of clinical trials, it is imperative to comprehensively examine genomics data to better comprehend the role of immunity in different cancers in predicting response to therapy and in directing appropriate therapies. The approach we chose is to scrutinize the pathways and epigenetic factors predicted to drive immune infiltration in different cancer types using publicly available TCGA transcriptional and methylation datasets, along with accompanying clinico-pathological data...
2019: Advances in Cancer Research
https://read.qxmd.com/read/30885353/pembrolizumab-in-combination-with-ipilimumab-as-second-line-or-later-therapy-for-advanced-non-small-cell-lung-cancer-keynote-021-cohorts-d-and-h
#3
Matthew A Gubens, Lecia V Sequist, James P Stevenson, Steven F Powell, Liza C Villaruz, Shirish M Gadgeel, Corey J Langer, Amita Patnaik, Hossein Borghaei, Shadia I Jalal, Joseph Fiore, Sanatan Saraf, Harry Raftopoulos, Leena Gandhi
OBJECTIVES: Combination immunotherapy may result in improved antitumor activity compared with single-agent treatment. We report results from dose-finding and dose-expansion cohorts of the phase 1/2 KEYNOTE-021 study that evaluated combination therapy with anti‒programmed death 1 (PD-1) antibody pembrolizumab plus anti‒cytotoxic T-lymphocyte antigen-4 (CTLA-4) antibody ipilimumab in patients with previously treated advanced non-small-cell lung cancer (NSCLC). MATERIALS AND METHODS: Eligibility criteria stipulated histologically/cytologically confirmed advanced NSCLC and treatment failure on ≥1 prior systemic therapy (platinum-based chemotherapy or targeted therapy for patients with EGFR/ALK aberrations)...
April 2019: Lung Cancer: Journal of the International Association for the Study of Lung Cancer
https://read.qxmd.com/read/30878596/simultaneous-blocking-of-cd47-and-pd-l1-increases-innate-and-adaptive-cancer-immune-responses-and-cytokine-release
#4
Shu Lian, Ruizhi Xie, Yuying Ye, Xiaodong Xie, Shuhui Li, Yusheng Lu, Bifei Li, Yunlong Cheng, Vladimir L Katanaev, Lee Jia
BACKGROUND: Treatment multiple tumors by immune therapy can be achieved by mobilizing both innate and adaptive immunity. The programmed death ligand 1 (PD-L1; or CD274, B7-H1) is a critical "don't find me" signal to the adaptive immune system. Equally CD47 is a critical "don't eat me" signal to the innate immune system and a regulator of the adaptive immune response. METHOD: Both of CD47 and PD-L1 are overexpressed on the surface of cancer cells to enable to escape immune-surveillance...
March 14, 2019: EBioMedicine
https://read.qxmd.com/read/30877109/regulation-of-mirna-biogenesis-and-histone-modification-by-k63-polyubiquitinated-ddx17-controls-cancer-stem-like-features
#5
Shih-Han Kao, Wei-Chung Cheng, Yi-Ting Wang, Han-Tsang Wu, Han-Yu Yeh, Yu-Ju Chen, Ming-Hsui Tsai, Kou-Juey Wu
Markers of cancer stemness predispose patients to tumor aggressiveness, drug and immunotherapy resistance, relapse, and metastasis. DDX17 is a co-factor of the Drosha-DGCR8 complex in miRNA biogenesis and transcriptional coactivator and has been associated with cancer stem-like properties. However, the precise mechanism by which DDX17 controls cancer stem-like features remains elusive. Here we show that the E3 ligase HectH9 mediated K63-polyubiquitination of DDX17 under hypoxia to control stem-like properties and tumor-initiating capabilities...
March 15, 2019: Cancer Research
https://read.qxmd.com/read/30877100/circulating-tumor-dna-provides-a-sneak-peek-into-treatment-responses-in-non-small-cell-lung-cancer
#6
Tao Zou, Matthew Meyerson
Circulating tumor DNA (ctDNA) holds great promise as a noninvasive diagnostic tool to guide treatment for patients with lung cancer. Two studies by Phallen and colleagues and Anagnostou and colleagues correlated sensitive measures of ctDNA with clinical responses to tyrosine kinase inhibitors (TKI) and immune checkpoint inhibitors, respectively, in patients with non-small cell lung cancer (NSCLC). Together, these studies further highlight the potential clinical utility of serial ctDNA monitoring in patients with NSCLC undergoing treatment with both targeted therapies and immunotherapies...
March 15, 2019: Cancer Research
https://read.qxmd.com/read/30874964/the-role-of-surgery-in-management-of-locally-advanced-non-small-cell-lung-cancer
#7
REVIEW
Darren S Bryan, Jessica S Donington
Patients with locally advanced non-small cell lung cancer (NSCLC) are treated for cure, but treatment decisions are not straightforward. Chemotherapy is essential due to the high risk of systemic relapse, but local therapy is also required for cure. In the small subset of stage III patients with N0 or N1 disease, surgery is typically the initial therapy and extended resections are frequent. The majority of IIIA patients present with N2 disease and treatment paradigms for these patients are controversial, particularly concerning the role of resection...
March 14, 2019: Current Treatment Options in Oncology
https://read.qxmd.com/read/30869543/the-role-of-immune-checkpoint-inhibitors-in-advanced-non-small-cell-lung-cancer
#8
Nikolaos F Pistamaltzian, Vassilis Georgoulias, Athanasios Kotsakis
Cancer immunotherapy represents a major therapeutic breakthrough. Immune checkpoint inhibitors alone or in the context of a combination are considered the new standard of care in advanced non-small cell lung cancer (NSCLC). Areas covered: This review explains the biologic rationale behind the implementation of immune checkpoint inhibitors for the therapy of advanced NSCLC. It provides a detailed description of the clinical trials that have studied the various agents now in use and the results that lead to the currently approved indications...
March 14, 2019: Expert Review of Respiratory Medicine
https://read.qxmd.com/read/30868747/patterns-of-care-for-stage-iii-non-small-cell-lung-cancer-in-australia
#9
REVIEW
Phillip Parente, Bryan A Chan, Brett G M Hughes, Kevin Jasas, Rohit Joshi, Steven Kao, Fiona Hegi-Johnson, Rina Hui, Sara McLaughlin-Barrett, Ina Nordman, Emily Stone
Stage III non-small cell lung cancer (NSCLC) makes up a third of all NSCLC cases and is potentially curable. Despite this 5-year survival rates remain between 15% and 20% with chemoradiation treatment alone given with curative intent. With the recent exciting breakthroughs in immunotherapy use (durvalumab) for stage III NSCLC, further improvements in patient survival can be expected. Most patients with stage III NSCLC present initially to their general practitioner (GP). The recommended time from GP referral to first specialist appointment is less than 14 days with treatment initiated within 42 days...
March 14, 2019: Asia-Pacific Journal of Clinical Oncology
https://read.qxmd.com/read/30866032/new-developments-in-neoadjuvant-therapy-for-lung-cancer
#10
Paul A Bunn, Erin Schenk, Jose Pacheco, Anastasios Dimou
Lung cancer is the leading cause of cancer death in the United States and worldwide. While most patients present with advanced metastatic disease for which a cure is elusive, increased use of spiral CT screening has led to identification of more early-stage patients who can be treated. At the same time, immunotherapy and new targeted therapies have improved survival in advanced disease. These new therapies are now being studied in the neoadjuvant and adjuvant settings to reduce systemic recurrences and improve cure rates...
March 13, 2019: Oncology (Williston Park, NY)
https://read.qxmd.com/read/30865033/treatment-of-oncogene-driven-non-small-cell-lung-cancer
#11
Elisabeth A Kastelijn, Adrianus J de Langen, Bas J M Peters
PURPOSE OF REVIEW: With the development of targeted therapies, the treatment strategy of patients with advanced or metastatic non-small cell lung cancer (NSCLC) has changed tremendously. In this review, we focus on the different aspects of the treatment of oncogene-driven NSCLC. RECENT FINDINGS: Patients with an EGFR or ALK alteration show a better clinical outcome with tyrosine kinase inhibitor (TKI) treatment compared to chemotherapy.Patients with a ROS1 rearrangement or a BRAF V600E mutation show favorable clinical outcome with TKI treatment compared to chemotherapy, although randomized trials are not available...
March 6, 2019: Current Opinion in Pulmonary Medicine
https://read.qxmd.com/read/30864713/cd1d-highly-expressed-on-dcs-reduces-lung-tumor-burden-by-enhancing-antitumor-immunity
#12
Yifan Li, Chujun Zhao, Jiajing Liu, Zhou Lu, Mingfang Lu, Jie Gu, Ronghua Liu
Dendritic cells (DCs), as professional antigen‑presenting cells are essential for the initial activation of adaptive antitumor immunity. CD1d is considered to present phospholipid and glycosphingolipid antigens to NKT cells. However, it is currently unknown whether CD1d expression on DCs is capable of enhancing antitumor immunity, particularly T‑cell related immunity. We observed that CD1d was predominantly expressed on DCs in 3LL tumor‑bearing mice, whilst a deficiency of CD1d promoted tumor growth. Notably, CD1d expression on DCs was not only required for presenting antigen to NKT cells, but also markedly promoted CD4+T and CD8+T cell activation, particularly cytotoxic T cells...
February 28, 2019: Oncology Reports
https://read.qxmd.com/read/30864326/a-repository-of-microbial-marker-genes-related-to-human-health-and-diseases-for-host-phenotype-prediction-using-microbiome-data
#13
Wontack Han, Yuzhen Ye
The microbiome research is going through an evolutionary transition from focusing on the characterization of reference microbiomes associated with different environments/hosts to the translational applications, including using microbiome for disease diagnosis, improving the effcacy of cancer treatments, and prevention of diseases (e.g., using probiotics). Microbial markers have been identified from microbiome data derived from cohorts of patients with different diseases, treatment responsiveness, etc, and often predictors based on these markers were built for predicting host phenotype given a microbiome dataset (e...
2019: Pacific Symposium on Biocomputing
https://read.qxmd.com/read/30864018/strategies-to-overcome-acquired-resistance-to-egfr-tki-in-the-treatment-of-non-small-cell-lung-cancer
#14
REVIEW
J Gao, H-R Li, C Jin, J-H Jiang, J-Y Ding
Epidermal growth factor receptor tyrosine kinase inhibitor (EGFR TKI) represents a paradigm shift in the treatment of non-small cell lung cancer (NSCLC) patients and has been the first-line therapy in clinical practice. While erlotinib, gefitinib and afatinib have achieved superior efficacy in terms of progression-free survival and overall survival compared with conventional chemotherapy in NSCLC patients, most people inevitably develop acquired resistance to them, which presents another challenge in the treatment of NSCLC...
March 12, 2019: Clinical & Translational Oncology
https://read.qxmd.com/read/30862891/real-world-evidenceand-clinical-observations-of-the-treatment-of-advanced-non-small-cell-lung-cancer-with-pd-1-pd-l1-inhibitors
#15
Peng Song, Jingcheng Zhang, Congcong Shang, Li Zhang
To summarize the therapeutic effects of PD-1/PD-L1 inhibitors on patients with advanced non-small cell lung cancer (NSCLC) in a real-world setting, we attempted to identify potential molecular biomarkers or clinical factors that reflected the therapeutic effect. The medical records of patients with non-small cell lung cancer who were treated with PD-1/PD-L1 inhibitors were obtained from the outpatient department or inpatient department of Peking Union Medical College Hospital from August 1, 2015, to January 1, 2018...
March 12, 2019: Scientific Reports
https://read.qxmd.com/read/30860657/dramatic-response-to-nivolumab-after-local-radiotherapy-in-pulmonary-pleomorphic-carcinoma-with-rapid-progressive-post-surgical-recurrence
#16
Daizo Yaguchi, Motoshi Ichikawa, Masao Ito, Sawako Okamoto, Hayata Kimura, Kazuko Watanabe
Pulmonary pleomorphic carcinoma (PPC) is resistant to anticancer drug treatment, outcomes are poor, and no standard therapy has been established. High PD-L1 expression has been found in PPCs, suggesting the possible efficacy of an immune checkpoint inhibitor (ICI) in cancer immunotherapy; however, this approach requires further investigation through case accumulation. Herein, we report a case of rapid recurrence and progression of PPC early after surgery in a 70-year-old male ex-smoker. Surgery was performed for lung cancer of the right lower lobe, and a pathological examination indicated primary PPC with high PD-L1 expression (tumor proportion score: 90%)...
March 12, 2019: Thoracic Cancer
https://read.qxmd.com/read/30860438/recent-clinical-trials-of-immunotherapy-in-non-small-cell-lung-cancer
#17
Stavros Gkolfinopoulos, Giannis Mountzios
No abstract text is available yet for this article.
April 2019: Immunotherapy
https://read.qxmd.com/read/30855195/immunotherapy-for-small-cell-lung-cancer-mechanisms-of-resistance
#18
Gerhard Hamilton, Barbara Rath
Small cell lung cancer (SCLC) is a highly malignant disease with a dismal prognosis that is currently being tested for theclinical activity of checkpoint inhibitors. SCLC is associated with smoking and exhibits a high mutational burden. However, low expression of PD-L1 and MHC antigens, as well low levels of immune cell infiltration and rapid tumor progress seems to limit the efficacy of anticancer immunity. Nevertheless, long-term survival was reported from studies using anti-PD-1/PD-L1 and CTLA-4 agents. Areas covered: Data of clinical trials of checkpoint inhibitors in SCLC show lower success rates compared to NSCLC...
March 11, 2019: Expert Opinion on Biological Therapy
https://read.qxmd.com/read/30854949/genotype-driven-therapy-for-non-small-cell-lung-cancer-resistance-pan-inhibitors-and-immunotherapy
#19
Sitanshu S Singh, Achyut Dahal, Leeza Shrestha, Seetharama D Jois
Eighty-five percent of patients with lung cancer present with non-small cell lung cancer (NSCLC). Targeted therapy approaches are promising treatments for lung cancer. However, despite the development of targeted therapies using tyrosine kinase inhibitors (TKI) as well as monoclonal antibodies, the five-year relative survival rate for lung cancer patients is still only 18%, and patients inevitably become resistant to therapy. Mutations in Kirsten ras sarcoma viral homolog (KRAS) and epidermal growth factor receptor (EGFR) are the two most common genetic events in lung adenocarcinoma; they account for 25% and 20% of cases, respectively...
February 22, 2019: Current Medicinal Chemistry
https://read.qxmd.com/read/30854794/the-immune-microenvironment-in-non-small-cell-lung-cancer-is-predictive-of-prognosis-after-surgery
#20
Åsa Kristina Öjlert, Ann Rita Halvorsen, Daniel Nebdal, Marius Lund-Iversen, Steinar Solberg, Odd Terje Brustugun, Ole Christian Lingjaerde, Åslaug Helland
The impact of the tumor immune microenvironment on overall survival in non-small cell lung cancer (NSCLC) has been studied, but there is little information on its relevance for risk of relapse after surgery. Understanding more about the immune microenvironment in previously untreated NSCLC could help in identifying high-risk patients and patients more likely to benefit from neoadjuvant/ adjuvant immunotherapy. Here, we examined gene expression in 399 surgically-derived NSCLC samples and 47 samples from normal lung, using Agilent microarray and RNA sequencing...
March 10, 2019: Molecular Oncology
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