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Immunotherapy for lung cancer

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https://www.readbyqxmd.com/read/29677240/uveal-effusion-after-immune-checkpoint-inhibitor-therapy
#1
Merina Thomas, Stephen T Armenti, M Bernadete Ayres, Hakan Demirci
Importance: Immune checkpoint inhibitors, including antiprogrammed cell death protein-1 (anti-PD-1) and antiprogrammed cell death ligand-1 (anti-PD-L1) monoclonal antibodies, have recently been introduced as a promising new immunotherapy for solid cancers. The adverse effects typically include inflammation of the skin, endocrine, and gastrointestinal systems. Objective: To describe 3 patients who developed uveal effusion after initiating anti-PD-1 and anti-PD-L1 monoclonal antibody therapy...
April 12, 2018: JAMA Ophthalmology
https://www.readbyqxmd.com/read/29675101/a-network-meta-analysis-comparing-the-efficacy-and-safety-of-anti-pd-1-with-anti-pd-l1-in-non-small-cell-lung-cancer
#2
Wei You, Mei Liu, Ji-Dong Miao, Yu-Qian Liao, Yi-Bing Song, Dian-Kun Cai, Yang Gao, Hao Peng
Background : This network meta-analysis aimed at comparing anti-programmed death 1 (anti-PD-1) with anti-programmed death ligand 1(anti-PD-L1) immunotherapy in patients with metastatic, previously treated non-small cell lung cancer (NSCLC) who failed first-line treatment. Methods : We searched electronic databases to identify all eligible clinical trials. End-points included overall survival (OS), progression-free survival (PFS) and objective response. Hazard ratios (HRs) or odds ratios (ORs) and corresponding 95% confidence intervals (CIs) were extracted...
2018: Journal of Cancer
https://www.readbyqxmd.com/read/29674449/induction-of-antitumor-cytotoxic-lymphocytes-using-engineered-human-primary-blood-dendritic-cells
#3
Long Wu, Huan Zhang, Yixing Jiang, Robert C Gallo, Hua Cheng
Dendritic cell (DC)-based cancer immunotherapy has achieved modest clinical benefits, but several technical hurdles in DC preparation, activation, and cancer/testis antigen (CTA) delivery limit its broad applications. Here, we report the development of immortalized and constitutively activated human primary blood dendritic cell lines (ihv-DCs). The ihv-DCs are a subset of CD11c+ /CD205+ DCs that constitutively display costimulatory molecules. The ihv-DCs can be genetically modified to express human telomerase reverse transcriptase (hTERT) or the testis antigen MAGEA3 in generating CTA-specific cytotoxic T lymphocytes (CTLs)...
April 19, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29672849/baseline-neutrophilia-derived-neutrophil-to-lymphocyte-ratio-dnlr-platelet-to-lymphocyte-ratio-plr-and-outcome-in-non-small-cell-lung-cancer-nsclc-treated-with-nivolumab-or-docetaxel
#4
Alessandro Russo, Tindara Franchina, Giuseppina R R Ricciardi, Alessandra Battaglia, Antonino Scimone, Rosa Berenato, Antonio Giordano, Vincenzo Adamo
Nivolumab is a novel therapeutic option in NSCLC, associated with a significant survival gain compared with Docetaxel. However, predictive biomarkers are lacking. The presence of systemic inflammation has been correlated with poor outcome in many cancer types. We aimed to evaluate whether there is a correlation between some indicators of inflammation and response to Nivolumab or Docetaxel in pre-treated NSCLCs. Data of 62 patients receiving Nivolumab or Docetaxel were analyzed. Baseline neutrophilia and thrombocytosis were not associated with response...
April 19, 2018: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/29667271/syndrome-and-outcome-of-antibody-negative-limbic-encephalitis
#5
Francesc Graus, Domingo Escudero, Laura Oleaga, Jordi Bruna, Alberto Villarejo-Galende, Jordi Ballabriga, María Inés Barceló, Francisco Gilo, Stoyan Popkirov, Pavel Stourac, Josep Dalmau
OBJECTIVE: To report the clinical characteristics of 12 patients with limbic encephalitis (LE) who were antibody-negative after a comprehensive immunological study. METHODS: Review of clinical records of 163 patients with LE. Immunohistochemistry on rat brain, cultured neurons, and cell-based assays were used to identify neuronal autoantibodies. Patients were included if 1) there was adequate clinical, CSF, and MRI information to classify the syndrome as LE, 2) MRI images were accesible for central review, and 3) serum and CSF were available and confirmed negative for neuronal antibodies...
April 18, 2018: European Journal of Neurology: the Official Journal of the European Federation of Neurological Societies
https://www.readbyqxmd.com/read/29667169/expression-of-scavenger-receptor-marco-defines-a-targetable-tumor-associated-macrophage-subset-in-non-small-cell-lung-cancer
#6
Linnéa La Fleur, Vanessa F Boura, Andrey Alexeyenko, Anders Berglund, Victor Pontén, Johanna Sm Mattsson, Dijana Djureinovic, Johan Persson, Hans Brunnström, Johan Isaksson, Eva Brandén, Hirsh Koyi, Patrick Micke, Mikael Ci Karlsson, Johan Botling
Tumor-associated macrophages (TAMs) are attractive targets for immunotherapy. Recently, studies in animal models showed that treatment with an anti-TAM antibody directed against the scavenger receptor MARCO resulted in suppression of tumor growth and metastatic dissemination. Here we investigated the expression of MARCO in relation to other macrophage markers and immune pathways in a non-small cell lung cancer (NSCLC) cohort (n=352). MARCO, CD68, CD163, MSR1 and programmed death ligand-1 (PD-L1) were analyzed by immunohistochemistry and immunofluorescence, and associations to other immune cells and regulatory pathways were studied in a subset of cases (n=199) with available RNA-seq data...
April 18, 2018: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/29666811/immune-checkpoint-pathways-in-non-small-cell-lung-cancer
#7
REVIEW
Young Kwang Chae, Ayush Arya, Wade Iams, Marcello Cruz, Nisha Mohindra, Victoria Villaflor, Francis J Giles
Immunotherapy has evolved at a phenomenal pace in cancer therapeutics. This has primarily been fueled by the much perceived necessity to procure an alternative to current standard of care chemotherapy agents, owing to several concerns such as treatment-related toxicity and poor long-term survival associated with the same. The knowledge of various mechanisms involved in regulation of immune response to cancer cells has served a fundamental role in identifying key molecules through which immune cell activity may be modulated...
March 2018: Annals of Translational Medicine
https://www.readbyqxmd.com/read/29666732/renal-tubular-acidosis-an-adverse-effect-of-pd-1-inhibitor-immunotherapy
#8
Sandy El Bitar, Chanudi Weerasinghe, Elie El-Charabaty, Marcel Odaimi
Immune checkpoint blockade therapy is gaining popularity among oncologists for treatment of solid and hematologic malignancies. The widespread use of these agents resulted in increasing incidence of renal immune-related adverse events. Reported renal toxicity described so far includes acute interstitial nephritis, minimal change disease, and immune complex glomerulonephritis. We report the case of a 79-year-old female with metastatic non-small cell lung cancer on anti-PD-1 therapy nivolumab. After the 4th administration of nivolumab, the treatment course was complicated with normal anion gap metabolic acidosis...
2018: Case Reports in Oncological Medicine
https://www.readbyqxmd.com/read/29666402/expression-of-kk-lc-1-a-cancer-testis-antigen-at-non-tumour-sites-of-the-stomach-carrying-a-tumour
#9
Takashi Fukuyama, Nobue Futawatari, Rui Yamamura, Taiga Yamazaki, Yoshinobu Ichiki, Akira Ema, Hideki Ushiku, Yatsushi Nishi, Yoshihito Takahashi, Toshikazu Otsuka, Hitoshi Yamazaki, Wasaburo Koizumi, Kosei Yasumoto, Noritada Kobayashi
Kita-Kyushu lung cancer antigen-1 (KK-LC-1) is a cancer/testis antigen (CTA) and predominant target for cancer immunotherapy. Our previous study indicated that KK-LC-1 was expressed in 82% of gastric cancers, and also in 79% of early stage of gastric cancers, with a correlation to Helicobacter pylori (H. pylori) infection. In addition, we found that KK-LC-1 was occasionally expressed at non-tumour sites of stomachs carrying tumours. Here, we investigated the characteristics of KK-LC-1 expression at non-tumour sites and the clinical utility of these phenomena...
April 17, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29662549/tumour-necrosis-factor-interferon-gamma-and-interleukins-as-predictive-markers-of-antiprogrammed-cell-death-protein-1-treatment-in-advanced-non-small-cell-lung-cancer-a-pragmatic-approach-in-clinical-practice
#10
Efimia Boutsikou, Kalliopi Domvri, Georgia Hardavella, Dora Tsiouda, Konstantinos Zarogoulidis, Theodoros Kontakiotis
Background: The emergence of novel antiprogrammed cell death protein-1 (PD-1) inhibitors in non-small cell lung cancers (NSCLC) has revolutionized the therapeutic landscape of this disease. Although overall survival (OS) has improved in the first- and second-line therapy settings for advanced NSCLC, the benefit is not universal. In a climate of global scrutiny for healthcare costs and potential for toxicities related to immunotherapy, appropriate patient selection is crucial. The aim of this study was to evaluate potential prognostic and predictive biomarkers interferon-gamma (IFN-γ), tumour necrosis factor-alpha (TNF-α) and a panel of interleukins (ILs) in the peripheral blood, and assess any correlation with response to anti-PD-1 inhibition, progression-free survival and OS in NSCLC patients...
2018: Therapeutic Advances in Medical Oncology
https://www.readbyqxmd.com/read/29662547/pd-l1-expression-testing-in-non-small-cell-lung-cancer
#11
REVIEW
Cristina Teixidó, Noelia Vilariño, Roxana Reyes, Noemí Reguart
In recent years, immunotherapy has revolutionized and changed the standard of care in patients with advanced non-small cell lung cancer (NSCLC). Immune checkpoint inhibitors, fundamentally those that act by blocking the programmed cell death receptor-1 (PD-1) and its ligand the programmed cell death ligand-1 (PD-L1) have emerged as novel treatment strategies in NSCLC, demonstrating undoubted superiority over chemotherapy in terms of efficacy. Several of these immune checkpoint modulators have recently gained regulatory approval for the treatment of advanced NSCLC, such as nivolumab, atezolizumab and pembrolizumab in first-line (only the latter) and second-line settings, and more recently, durvalumab as maintenance after chemoradiotherapy in locally advanced disease...
2018: Therapeutic Advances in Medical Oncology
https://www.readbyqxmd.com/read/29662546/combination-of-immunotherapy-with-chemotherapy-and-radiotherapy-in-lung-cancer-is-this-the-beginning-of-the-end-for-cancer
#12
REVIEW
Chiara Lazzari, Niki Karachaliou, Alessandra Bulotta, Mariagrazia Viganó, Aurora Mirabile, Elena Brioschi, Mariacarmela Santarpia, Luca Gianni, Rafael Rosell, Vanesa Gregorc
Immune checkpoint inhibitors have significantly improved overall survival with an acceptable safety profile in a substantial proportion of non-small cell lung cancer (NSCLC) patients. However, not all patients are sensitive to immune checkpoint blockade and, in some cases, programmed death 1 (PD-1) or programmed death ligand 1 (PD-L1) inhibitors accelerate tumor progression. Several combination strategies are under evaluation, including the concomitant or sequential evaluation of chemotherapy or radiotherapy with immunotherapy...
2018: Therapeutic Advances in Medical Oncology
https://www.readbyqxmd.com/read/29661758/high-tmb-predicts-immunotherapy-benefit-in-nsclc
#13
(no author information available yet)
The first data from the phase III CheckMate-227 trial of ipilimumab plus nivolumab for the treatment of non-small cell lung cancer suggests that the two drugs boost progression-free survival in patients with a high tumor mutation burden. After 1 year, progression-free survival was 43% for patients treated with the checkpoint inhibitor combination, compared with 13% for patients treated with chemotherapy.
April 16, 2018: Cancer Discovery
https://www.readbyqxmd.com/read/29659925/tobacco-smoking-associated-alterations-in-the-immune-microenvironment-of-squamous-cell-carcinomas
#14
Alexis Desrichard, Fengshen Kuo, Diego Chowell, Ken-Wing Lee, Nadeem Riaz, Richard J Wong, Timothy A Chan, Luc G T Morris
Background: Tobacco smoking creates DNA damage, inducing mutations and potentially altering the tumor immune microenvironment. These types of genetic and immune microenvironment alterations are critical factors known to affect tumor response to immunotherapy. Here we analyze the association between the mutational signature of tobacco smoking, tumor mutational load, and metrics of immune activity in squamous cell carcinomas arising in the head and neck and lung. Methods: Using RNA and DNA sequencing data from The Cancer Genome Atlas head and neck (HNSC; n = 287) and lung (LUSC; n = 130) squamous cell carcinoma data sets and two independent gene expression data sets (HNSC, n = 136; LUSC, n = 75), we examined associations between the mutational smoking signature, mutation count, immune cell infiltration, cytolytic activity, and interferon-γ signaling...
April 11, 2018: Journal of the National Cancer Institute
https://www.readbyqxmd.com/read/29658011/a-listeria-derived-polypeptide-promotes-in-vivo-activation-of-nk-cells-for-antitumor-therapy
#15
Amber L Ortiz, Laurel L Lenz
Immunotherapies have shown promise in treatment of cancer, but more potent and targeted therapies are needed. Natural killer (NK) cells are lymphocytes with innate ability to recognize and lyse tumor cells. When activated, they also produce type II interferon (IFNγ) to orchestrate the activity of other immune cells. Strategies to elicit NK cell activation in vivo have potential usefulness in anti-tumor immunotherapies. Here, we report on a strategy to stimulate NK cell activation and anti-tumor activity in mice with established B16...
June 1, 2017: ImmunoHorizons
https://www.readbyqxmd.com/read/29656755/the-burden-of-lung-cancer-in-latin-america-and-challenges-in-the-access-to-genomic-profiling-immunotherapy-and-targeted-treatments
#16
REVIEW
Luis E Raez, Andrés F Cardona, Edgardo S Santos, Heath Catoe, Christian Rolfo, Gilberto Lopes, Carlos Barrios, Luis A Mas, Carlos Vallejos, Zyanya Lucia Zatarain-Barrón, Christian Caglevic, Oscar Arrieta
Lung cancer is a public health problem worldwide and Latin America (LATAM) cannot escape this reality. This malignant disease has not only a high prevalence in the region, but is also the main cause of cancer related deaths, and in other emerging countries, the incidence rates are still on the rise. Interestingly in most LATAM countries, lung cancer mortality has been decreasing in men but not in women, reflecting smoking patterns in countries such as Chile, Bolivia, and Brazil. Despite the fact that these issues are well known to government agencies, physicians and patients in the region, current efforts still fall behind those needed in order to face this problem of epidemic proportions...
May 2018: Lung Cancer: Journal of the International Association for the Study of Lung Cancer
https://www.readbyqxmd.com/read/29628498/tumor-infiltrating-b-cells-their-role-and-application-in-anti-tumor-immunity-in-lung-cancer
#17
REVIEW
Si-Si Wang, Wei Liu, Dalam Ly, Hao Xu, Limei Qu, Li Zhang
Evidence indicates that lung cancer development is a complex process that involves interactions between tumor cells, stromal fibroblasts, and immune cells. Tumor-infiltrating immune cells play a significant role in the promotion or inhibition of tumor growth. As an integral component of the tumor microenvironment, tumor-infiltrating B lymphocytes (TIBs) exist in all stages of cancer and play important roles in shaping tumor development. Here, we review recent clinical and preclinical studies that outline the role of TIBs in lung cancer development, assess their prognostic significance, and explore the potential benefit of B cell-based immunotherapy for lung cancer treatment...
April 8, 2018: Cellular & Molecular Immunology
https://www.readbyqxmd.com/read/29628312/alt-803-an-il-15-superagonist-in-combination-with-nivolumab-in-patients-with-metastatic-non-small-cell-lung-cancer-a-non-randomised-open-label-phase-1b-trial
#18
John M Wrangle, Vamsidhar Velcheti, Manish R Patel, Elizabeth Garrett-Mayer, Elizabeth G Hill, James G Ravenel, Jeffrey S Miller, Mohammad Farhad, Kate Anderton, Kathryn Lindsey, Michele Taffaro-Neskey, Carol Sherman, Samantha Suriano, Marzena Swiderska-Syn, Amy Sion, Joni Harris, Andie R Edwards, Julie A Rytlewski, Catherine M Sanders, Erik C Yusko, Mark D Robinson, Carsten Krieg, William L Redmond, Jack O Egan, Peter R Rhode, Emily K Jeng, Amy D Rock, Hing C Wong, Mark P Rubinstein
BACKGROUND: Immunotherapy with PD-1 or PD-L1 blockade fails to induce a response in about 80% of patients with unselected non-small cell lung cancer (NSCLC), and many of those who do initially respond then develop resistance to treatment. Agonists that target the shared interleukin-2 (IL-2) and IL-15Rβγ pathway have induced complete and durable responses in some cancers, but no studies have been done to assess the safety or efficacy of these agonists in combination with anti-PD-1 immunotherapy...
April 5, 2018: Lancet Oncology
https://www.readbyqxmd.com/read/29627136/teipp-antigens-for-t-cell-based-immunotherapy-of-immune-edited-hla-class-i-low-cancers
#19
Koen A Marijt, Elien M Doorduijn, Thorbald van Hall
T-cell based immunotherapies through checkpoint blockade or adoptive transfer are effective treatments for a wide range of cancers like melanomas and lung carcinomas that harbor a high mutational load. The HLA class I and class II (HLA-I and HLA-II) presented neoantigens arise from genetic mutations in the cancerous cells and are ideal non-self targets for the T cell-based treatments. Although some cancer patients responded with complete regression, many others are irresponsive to checkpoint blockade treatments, or relapse after initial success...
April 4, 2018: Molecular Immunology
https://www.readbyqxmd.com/read/29623110/clinical-assessment-of-immune-related-adverse-events
#20
REVIEW
Aaron Sosa, Esther Lopez Cadena, Cristina Simon Olive, Niki Karachaliou, Rafael Rosell
Immunotherapy through checkpoint inhibitors is now standard practice for a growing number of cancer types, supported by overall improvement of clinical outcomes and better tolerance. One anti-CTLA-4 antibody (ipilimumab), two anti-PD-1 antibodies (pembrolizumab and nivolumab) and three anti-PD-L1 antibodies (atezolizumab, avelumab and durvalumab) have been approved for clear benefits across diverse trials. Adverse events of an immune nature associated with these agents frequently affect the skin, colon, endocrine glands, lungs and liver...
2018: Therapeutic Advances in Medical Oncology
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