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Clinical immunology and lung cancer

Eduardo Luis Callejas-Moraga, Alfredo Guillén-Del-Castillo, Ana María Marín-Sánchez, María Roca-Herrera, Eva Balada, Carles Tolosa-Vilella, Vicente Fonollosa-Pla, Carmen Pilar Simeón-Aznar
OBJECTIVES: To evaluate the clinical features and survival of patients with positive anti-RNA polymerase III (anti-RNAP III) in a Spanish single centre. METHODS: We analysed 221 patients with SSc according to LeRoy and Medsger criteria. Twenty-six patients with positivity for anti-RNAP III antibodies were compared with 195 negative patients. Epidemiological, clinical, immunological features and survival were analysed. RESULTS: In patients with anti-RNAP III positivity diffuse cutaneous SSc (dcSSc) subset was the most prevalent (20, 76...
February 11, 2019: Clinical and Experimental Rheumatology
Koichi Saruwatari, Ryo Sato, Shunya Nakane, Shinya Sakata, Koutaro Takamatsu, Takayuki Jodai, Remi Mito, Yuko Horio, Sho Saeki, Yusuke Tomita, Takuro Sakagami
BACKGROUND: Anti-programmed cell death 1 (PD-1) monoclonal antibodies (Abs) unleash an immune response to cancer. However, a disruption of the immune checkpoint function by blocking PD-1/PD-ligand 1(PD-L1) signaling may trigger myasthenia gravis (MG) as a life-threatening immune-related adverse event. MG is a neuromuscular disease and is closely associated with being positive for anti-acetylcholine receptor (anti-AChR) Abs, which are high specific and diagnostic Abs for MG. METHODS: A 72-year-old man was diagnosed with chemotherapy-refractory lung squamous cell carcinoma and nivolumab was selected as the third-line regimen...
January 24, 2019: Cancers
Chun-Tong Bao, Jia-Meng Xiao, Bai-Jun Liu, Jian-Fang Liu, Ri-Ning Zhu, Peng Jiang, Lei Li, Paul Richard Langford, Lian-Cheng Lei
Actinobacillus pleuropneumoniae (APP) causes porcine pleuropneumonia, a disease responsible for substantial losses in the worldwide pig industry. In this study, outbred Kunming (KM) and Institute of Cancer Research (ICR) mice were evaluated as alternative mice models for APP research. After intranasal infection of serotype 5 reference strain L20, there was less lung damage and a lower clinical sign score in ICR compared to KM mice. However, ICR mice showed more obvious changes in body weight loss, the amount of immune cells (such as neutrophils and lymphocytes) and cytokines (such as IL-6, IL-1β and TNF-α) in blood and bronchoalveolar lavage fluid (BALF)...
January 18, 2019: Microbial Pathogenesis
Pauline L de Goeje, Myrthe Poncin, Koen Bezemer, Margaretha E H Kaijen-Lambers, Harry Jm Groen, Egbert F Smit, Anne-Marie C Dingemans, Andre Kunert, Rudi W Hendriks, Joachim G Aerts
INTRODUCTION: Chemotherapy has long been the standard treatment for advanced stage non-small cell lung cancer (NSCLC), but checkpoint inhibitors are now approved for use in several patient groups and combinations. To design optimal combination strategies, a better understanding of the immune modulatory capacities of conventional treatments is needed. Therefore, we investigated the immune-modulatory effects of paclitaxel/carboplatin/bevacizumab (PCB), focusing on immune populations associated with response to checkpoint inhibitors in peripheral blood...
January 14, 2019: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Srimoyee Ghosh, Geeta Sharma, Jon Travers, Sujatha Kumar, Justin Choi, H Toni Jun, Marilyn Kehry, Sridhar Ramaswamy, David Jenkins
Progressive upregulation of checkpoints on tumor infiltrating lymphocytes promotes an immunosuppressive tumor microenvironment, severely compromising tumor immunity. Lymphocyte activation gene-3 (LAG-3) is a co-inhibitory receptor associated with impaired T cell function and is frequently co-expressed with programmed cell death protein-1 (PD-1) in the context of human cancers. Targeting LAG-3 in conjunction with PD-1 thus represents a strategy to amplify and broaden the therapeutic impact of PD-1 blockade alone...
December 26, 2018: Molecular Cancer Therapeutics
Saman Maleki Vareki
Tumors responding to immune checkpoint inhibitors (ICIs) have a higher level of immune infiltrates and/or an Interferon (IFN) signature indicative of a T-cell-inflamed phenotype. Melanoma and lung cancer demonstrate high response rates to ICIs and are commonly referred to as "hot tumors". These are in sharp contrast to tumors with low immune infiltrates called "cold tumors" or non-T-cell-inflamed cancers, such as those from the prostate and pancreas. Classification of tumors based on their immune phenotype can partially explain clinical response to ICIs...
December 27, 2018: Journal for Immunotherapy of Cancer
Florian Wirsdörfer, Simone de Leve, Verena Jendrossek
In recent decades, technical advances in surgery and radiotherapy, as well as breakthroughs in the knowledge on cancer biology, have helped to substantially improve the standard of cancer care with respect to overall response rates, progression-free survival, and the quality of life of cancer patients. In this context, immunotherapy is thought to have revolutionized the standard of care for cancer patients in the long term. For example, immunotherapy approaches such as immune checkpoint blockade are currently increasingly being used in cancer treatment, either alone or in combination with chemotherapy or radiotherapy, and there is hope from the first clinical trials that the appropriate integration of immunotherapy into standard care will raise the success rates of cancer therapy to a new level...
December 21, 2018: International Journal of Molecular Sciences
E Eisenhuber, C Schaefer-Prokop, G Mostbeck
Lung cancer is a histologically, immunologically and therefore morphologically and functionally very heterogeneous group of neoplasms with the highest cancer mortality worldwide. Therefore, the range of diseases mimicking lung cancer is also very broad and includes congenital, infectious and inflammatory changes as well as other benign space-occupying lesions and other primary and secondary pulmonary neoplasms. The difficulty in radiology lies in the ability to diagnose lung cancer with a high degree of certainty...
December 14, 2018: Der Radiologe
Biagio Ricciuti, Carlo Genova, Andrea De Giglio, Maria Bassanelli, Maria Giovanna Dal Bello, Giulio Metro, Marta Brambilla, Sara Baglivo, Francesco Grossi, Rita Chiari
PURPOSE: Immune-checkpoint inhibitors (ICIs) represent the standard of care for platinum-pretreated advanced non-small cell lung cancer patients. Patients treated with ICIs may experience immune-related adverse events (irAEs), that might reflect antitumor responses. Here we evaluated nivolumab efficacy according to the development of irAEs. METHODS: We conducted a multicenter retrospective study of patients with advanced NSCLC treated with nivolumab between October 2013 and September 2017...
December 1, 2018: Journal of Cancer Research and Clinical Oncology
Mei-Chun Cai, Minjiang Chen, Pengfei Ma, Jie Wu, Haijiao Lu, Shengzhe Zhang, Jin Liu, Xiaojing Zhao, Guanglei Zhuang, Zhuang Yu, Yujie Fu
Somatic KEAP1-NRF2 pathway alterations are frequently detected in both lung adenocarcinomas and squamous cell carcinomas. However, the biological characteristics and molecular subtypes of KEAP1/NRF2-mutant lung cancer remain largely undefined. Here, we performed a stepwise, integrative analytic and experimental interrogation of primary tumors and cancer cell lines harboring KEAP1 or NFE2L2 (encoding NRF2) gene mutations. First, we discovered that KEAP1/NRF2-mutant lung cancer presented APOBEC-mediated mutational signatures, impaired tumor angiogenesis, elevated hypoxic stress and deficient immune-cell infiltrates...
November 8, 2018: International Journal of Cancer. Journal International du Cancer
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
Luis Aj Mur, Sharon A Huws, Simon Js Cameron, Paul D Lewis, Keir E Lewis
The lung microbiome has been shown to reflect a range of pulmonary diseases-for example: asthma, chronic obstructive pulmonary disease (COPD) and cystic fibrosis. Studies have now begun to show microbiological changes in the lung that correlate with lung cancer (LC) which could provide new insights into lung carcinogenesis and new biomarkers for disease screening. Clinical studies have suggested that infections with tuberculosis or pneumonia increased the risk of LC possibly through inflammatory or immunological changes...
2018: Ecancermedicalscience
Francesco Facchinetti, Paola Bordi, Alessandro Leonetti, Sebastiano Buti, Marcello Tiseo
Programed cell death-1/programed death ligand-1 (PD-1/PD-L1) blockade represents an affirmed reality in the treatment of advanced non-small-cell lung cancer (NSCLC) patients. Atezolizumab, an anti-PD-L1 agent, figures among the drugs that provide previously unenvisaged outcomes in the pretreated setting of metastatic NSCLC. Increasing evidence vouches for the early administration of PD-1/PD-L1 blockers in untreated patients, encompassing atezolizumab combinations with chemotherapy and the anti-angiogenic agent bevacizumab...
2018: Drug Design, Development and Therapy
Di Huang, Jianing Chen, Linbin Yang, Qian Ouyang, Jiaqian Li, Liyan Lao, Jinghua Zhao, Jiang Liu, Yiwen Lu, Yue Xing, Fei Chen, Fengxi Su, Herui Yao, Qiang Liu, Shicheng Su, Erwei Song
Activation-induced cell death (AICD) of T lymphocytes can be exploited by cancers to escape immunological destruction. We demonstrated that tumor-specific cytotoxic T lymphocytes (CTLs) and type 1 helper T (TH 1) cells, rather than type 2 helper T cells and regulatory T cells, were sensitive to AICD in breast and lung cancer microenvironments. NKILA, an NF-κB-interacting long noncoding RNA (lncRNA), regulates T cell sensitivity to AICD by inhibiting NF-κB activity. Mechanistically, calcium influx in stimulated T cells via T cell-receptor signaling activates calmodulin, thereby removing deacetylase from the NKILA promoter and enhancing STAT1-mediated transcription...
October 2018: Nature Immunology
Steven Lehrer, Peter H Rheinstein
BACKGROUND: One aspect of smoking and lung cancer that has not been closely examined, is that regarding genes that may predispose to tobacco dependence. Smoking and mental illness are tightly linked, apparently the result of smokers using cigarettes to self-medicate for mental problems. The gene for solute carrier family 18 member A1 (vesicular monoamine transporter; SLC18A1) is of particular interest in this regard because of its association with schizophrenia, autism and bipolar illness as well as with cancer...
September 2018: Cancer Genomics & Proteomics
Fathia Mami-Chouaib, Charlotte Blanc, Stéphanie Corgnac, Sophie Hans, Ines Malenica, Clémence Granier, Isabelle Tihy, Eric Tartour
CD8+ T lymphocytes are the major anti-tumor effector cells. Most cancer immunotherapeutic approaches seek to amplify cytotoxic T lymphocytes (CTL) specific to malignant cells. A recently identified subpopulation of memory CD8+ T cells, named tissue-resident memory T (TRM ) cells, persists in peripheral tissues and does not recirculate. This T-cell subset is considered an independent memory T-cell lineage with a specific profile of transcription factors, including Runx3+ , Notch+ , Hobit+ , Blimp1+ , BATF+ , AHR+ , EOMESneg and Tbetlow ...
September 4, 2018: Journal for Immunotherapy of Cancer
Yushu Zhou, Baiming Zhao, Wanyin Wu, Xiaobing Yang, Shunqin Long, Hong Deng, Wenfeng He, Guiya Liao, Qiuping Li, Zhen Xie
BACKGROUND: Cancer-related fatigue (CRF) is the most common symptom in patients with advanced non-small cell lung cancer (NSCLC) undergoing treatment with chemotherapy. However, evidence upon which to base management strategies is scarce. Traditional Chinese Medicine (TCM) has been shown to be beneficial to patients with CRF. Chinese herbal injections should be administered under an evidence-based approach. This trial aims to assess the efficacy and safety of the addition of the Shenmai injection (SMI) to conventional therapy for CRF in NSCLC patients undergoing chemotherapy...
September 4, 2018: Trials
Alok Mishra, Mukesh Verma
Utilizing biology of PD-1: PD-L1 interaction related pathways for cancer immunotherapy is an emerging concept in cancer research. However, there is limited literature on epigenetic regulation of PD1 gene (PDCD1). Promising data from clinical trials of PD/PDl-1 immunotherapy in melanoma, renal cancers, colorectal and lung cancers has generated a lot of hope for successful treatment of patients. Immunotherapy in cancers has a significant role in strategizing NCI's Cancer Moonshot Program of US NIH and FDA policies...
2018: Methods in Molecular Biology
Simona Ferro, Veronica Huber, Licia Rivoltini
If immunotherapy is currently considered as a valid treatment strategy in oncology, the concept that cancer could be cured by the mere manipulation of the immune system was almost inconceivable until few years ago, particularly in lung cancer. The use of immune checkpoint inhibitors has instead demonstrated to mediate significant long-term disease control so to rapidly enter clinical practice and represent the basis for most of the combination approaches under development. In light of the revolutionary results achieved through the pivotal clinical trials and the large expectations about the possibility to further improve clinical benefit and discover novel therapeutic targets, it is becoming nowadays mandatory to increase our knowledge on the basics of immunology in lung cancer...
July 2018: Journal of Thoracic Disease
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 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
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