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https://www.readbyqxmd.com/read/29243049/high-pd-l1-expression-indicates-poor-prognosis-of-hiv-infected-patients-with-non-small-cell-lung-cancer
#1
Yusuke Okuma, Tsunekazu Hishima, Jumpei Kashima, Sadamu Homma
BACKGROUND: The status of antitumor immunity represented by the expression of programmed cell death-1 (PD-1)/programmed cell death-ligand 1 (PD-L1) and immune cell (IC) infiltration is unknown in HIV-infected patients with non-small cell lung cancer (NSCLC). METHODS: Fifteen HIV-infected patients with NSCLC were compared with 29 non-HIV-infected patients with NSCLC. Analysis of 13 propensity-score-matched patients in the two groups was also compared. The expression of PD-1/PD-L1 and tumor infiltration by CD4+, CD8+, and CD56+ immune cells were examined by immunohistochemistry; score of ≥ 2 was defined as positive...
December 14, 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/29241546/neutrophils-and-snail-orchestrate-the-establishment-of-a-pro-tumor-microenvironment-in-lung-cancer
#2
Julien Faget, Svenja Groeneveld, Gael Boivin, Martial Sankar, Nadine Zangger, Miguel Garcia, Nicolas Guex, Inti Zlobec, Loïc Steiner, Alessandra Piersigilli, Ioannis Xenarios, Etienne Meylan
Understanding the immune compartment of tumors facilitates the development of revolutionary new therapies. We used a Kras(G12D)-driven mouse model of lung cancer to establish an immune signature and identified a contribution of Gr1+ neutrophils to disease progression. Depletion experiments showed that Gr1+ cells (1) favor tumor growth, (2) reduce T cell homing and prevent successful anti-PD1 immunotherapy, and (3) alter angiogenesis, leading to hypoxia and sustained Snail expression in lung cancer cells. In turn, Snail accelerated disease progression and increased intratumoral Cxcl2 secretion and neutrophil infiltration...
December 12, 2017: Cell Reports
https://www.readbyqxmd.com/read/29238349/the-roles-of-glycodelin-in-cancer-development-and-progression
#3
REVIEW
Juan Cui, Yanguo Liu, Xiuwen Wang
Glycodelin is a kind of glycoprotein expressed in secretory endometrium, pregnancy deciduas, and amniotic fluid originally, which is vital for the maintenance of normal human reproductive activities. Recent researches have reported that glycodelin is specifically expressed in various malignancies, including female-specific cancers such as endometrial cancer, ovarian cancer and breast cancer, and non-gender specific cancers including lung cancer, and colon cancer, and glycodelin expression correlates with the diagnosis and prognosis of cancer patients...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29238207/advances-in-t-cell-checkpoint-immunotherapy-for-head-and-neck-squamous-cell-carcinoma
#4
REVIEW
Xinmeng Qi, Bo Jia, Xue Zhao, Dan Yu
Head and neck squamous cell carcinoma (HNSCC) has been found to be a complex group of malignancies characterized by their profound immunosuppression and high aggressiveness. In most cases of advanced HNSCC, treatment fails to obtain total cancer cure. Efforts are needed to develop new therapeutic approaches to improve HNSCC outcomes. In this light, T-cells "immune checkpoint" has attracted much attention in cancer immunotherapy. It has been broadly accepted that inhibitory T-cell immune checkpoints contribute to tumor immune escape through negative immune regulatory signals (cytotoxic T-lymphocyte-associated antigen 4 [CTLA-4], programmed cell death 1 [PD-1], B7-H3, and B7-H4, etc)...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/29238163/the-coexpression-of-multi-immune-inhibitory-receptors-on-t-lymphocytes-in-primary-non-small-cell-lung-cancer
#5
REVIEW
Wenjie Guo, Sihan Liu, Xiaoli Zhang, Yating Chen, Ruolan Qian, Ziyuan Zou, Xin Chen, Peng Luo
Non-small-cell lung cancer (NSCLC) is a common disease threatening the health of humankind. It has a low survival rate and a poor prognosis. Under normal circumstances, tumor infiltrating lymphocytes (TILs) play the main role in the antitumor process, but studies in recent years have found that NSCLC is capable of releasing various immunosuppressive factors, inducing the TILs to exhibit high expression of immune inhibitory receptors and relevant immunosuppressive factors. They can not only activate their own signal pathways but also block those of TILs, which causes inefficiency of tumor destruction...
2017: Drug Design, Development and Therapy
https://www.readbyqxmd.com/read/29234363/shenfu-injection-adjunct-with-platinum-based-chemotherapy-for-the-treatment-of-advanced-non-small-cell-lung-cancer-a-meta-analysis-and-systematic-review
#6
REVIEW
Ailing Cao, Hailang He, Mengxin Jing, Beibei Yu, Xianmei Zhou
Platinum-based chemotherapy is one of the standard treatments for non-small-cell lung cancer (NSCLC), while its high toxicity and limited clinical effects raise big concerns. Shenfu injection (SFI) has been commonly used as an adjutant chemotherapy drug for NSCLC in China. We ascertained the beneficial and adverse effects of SFI in combination with platinum-based chemotherapy for advanced NSCLC by using meta-analysis methods. The randomized controlled trials (RCTs) involving advanced NSCLC treatment with SFI plus platinum-based chemotherapy versus chemotherapy alone were searched on 6 medical databases up to February 2017...
2017: Evidence-based Complementary and Alternative Medicine: ECAM
https://www.readbyqxmd.com/read/29230503/concordance-between-the-response-evaluation-criteria-in-solid-tumors-version-1-1-and-the-immune-related-response-criteria-in-patients-with-non-small-cell-lung-cancer-treated-with-nivolumab-a-multicenter-retrospective-cohort-study
#7
Yuki Kataoka, Katsuya Hirano, Tomoko Narabayashi, Satoshi Hara, Daichi Fujimoto, Tae Tanaka, Noriyuki Ebi, Keisuke Tomii, Hiroshige Yoshioka
PURPOSE: The immune-related response criteria (irRC) were proposed to incorporate pseudo-progression. However, the association between the irRC and overall survival (OS) has yet to be evaluated in non-small cell lung cancer (NSCLC). Therefore, the purpose of this study is to evaluate the concordance between the response evaluation criteria in solid tumors (RECIST) version 1.1 and the irRC in patients with NSCLC treated with nivolumab, as well as, to determine the relationship between these two response criteria and OS...
December 11, 2017: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/29230210/checkpoint-blockade-toxicity-and-immune-homeostasis-in-the-gastrointestinal-tract
#8
REVIEW
Michael Dougan
Monoclonal antibodies targeting the regulatory immune "checkpoint" receptors CTLA-4, PD-1, and PD-L1 are now standard therapy for diverse malignancies including melanoma, lung cancer, and renal cell carcinoma. Although effective in many patients and able to induce cures in some, targeting these regulatory pathways has led to a new class of immune-related adverse events. In many respects, these immune toxicities resemble idiopathic autoimmune diseases, such as inflammatory bowel disease, autoimmune hepatitis, rheumatoid arthritis, and vitiligo...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29230122/the-role-of-checkpoint-inhibition-in-non-small-cell-lung-cancer
#9
REVIEW
Jonathan Lu, Robert A Ramirez
Background: The development of immune checkpoint inhibitors has revolutionized the treatment of cancer. Their use in non-small cell lung cancer (NSCLC) remains in its infancy, but rapid progress has been made in treating metastatic NSCLC. Methods: This article outlines the role of immune checkpoint inhibitors in the treatment of malignancy and reviews clinical trials of novel immunotherapies in the setting of metastatic NSCLC. Results: Traditional chemotherapy with a platinum-based doublet has long been the backbone in the treatment of metastatic NSCLC...
2017: Ochsner Journal
https://www.readbyqxmd.com/read/29228707/pd-l1-immunohistochemical-assays-for-assessment-of-therapeutic-strategies-involving-immune-checkpoint-inhibitors-in-non-small-cell-lung-cancer-a-comparative-study
#10
Hyojin Kim, Hyun Jung Kwon, Soo Young Park, Eunhyang Park, Jin-Haeng Chung
Although immune checkpoints inhibitors have exhibited promising activity in clinical trials in non-small cell lung cancer (NSCLC) patients, the current programmed cell death-ligand 1 (PD-L1) assays are inconsistent in terms of the staining analysis and scoring system used. To verify the interchangeability of the available PD-L1 assays, we performed immunohistochemistry using three antibody clones used in clinical trials (22C3, SP263, and SP142) and the E1L3N clone as a laboratory developed test for 97 resected NSCLC specimens...
November 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29225707/how-to-evaluate-the-immune-status-of-lung-cancer-patients-before-immunotherapy
#11
Joanna Domagala-Kulawik, Agata Raniszewska
Nowadays, cancer immunotherapy is a promising strategy in solid tumour treatment. It has become a breakthrough in achieving long-term survival in many advanced cases. The essence of modern immunotherapy is to improve the host antitumour immune defence. Currently, it is critically important to determine the biomarkers that could be helpful in planning this type of individual therapy. It has turned out that an important prognostic factor is the evaluation of inflammatory infiltration of the tumour mass, including the characteristics of populations of lymphocytes and macrophages, and the expression of suppressive and regulatory molecules...
December 2017: Breathe
https://www.readbyqxmd.com/read/29225480/role-of-afatinib-in-the-treatment-of-advanced-lung-squamous-cell-carcinoma
#12
REVIEW
Tiziana Vavalà
Lung cancer treatment has considerably changed over the last few years: the identification of druggable oncogenic alterations and innovative immunotherapic approaches granted lung cancer patients the possibility of more efficient and less toxic therapeutic options than chemotherapy. Nowadays, lung squamous cell carcinomas (SqCCs) patients have the chance to benefit from novel treatment alternatives, including immune checkpoint blockade and anti-angiogenic agents and, given positive trial results, from afatinib, a second generation tyrosine kinase inhibitor (TKI) that irreversibly antagonizes ErbB family tyrosine kinase receptors...
2017: Clinical Pharmacology: Advances and Applications
https://www.readbyqxmd.com/read/29223537/rankl-signaling-sustains-primary-tumor-growth-in-genetically-engineered-mouse-models-of-lung-adenocarcinoma
#13
Julien Faget, Caroline Contat, Nadine Zangger, Solange Peters, Etienne Meylan
HYPOTHESIS: Non-small cell lung cancer (NSCLC) is the leading cause of cancer mortality. Recent retrospective clinical analyses suggest that blocking the receptor activator of NF-κB (RANK) signaling pathway inhibits the growth of NSCLC and might represent a new treatment strategy. METHODS: RANK and RANKL expression in human lung adenocarcinoma was interrogated from publicly available gene expression datasets. Several genetically engineered mouse models were used to evaluate treatment efficacy of RANK-Fc to block RANKL, with primary tumor growth measured longitudinally using micro-computed tomography...
December 6, 2017: Journal of Thoracic Oncology
https://www.readbyqxmd.com/read/29222007/current-concepts-in-pathogenesis-diagnosis-and-management-of-smoking-related-interstitial-lung-diseases
#14
REVIEW
Anupam Kumar, Sujith V Cherian, Robert Vassallo, Eunhee S Yi, Jay H Ryu
Tobacco exposure results in various changes to the airways and lung parenchyma. While emphysema represents the more common injury pattern, in some individuals, cigarette smoke injures alveolar epithelial and other lung cells resulting in diffuse infiltrates and parenchymal fibrosis. Smoking can trigger interstitial injury patterns mediated via recruitment and inappropriate persistence of myeloid and other immune cells including eosinophils. As our understanding of the role of cigarette smoke constituents in triggering lung injury continues to evolve, so does our recognition of the spectrum of smoking-related interstitial lung changes...
December 5, 2017: Chest
https://www.readbyqxmd.com/read/29221287/anti-cancer-activity-of-dose-fractioned-mpe-bevacizumab-regimen-is-paralleled-by-immune-modulation-in-advanced-squamous-nslc-patients
#15
Pierpaolo Pastina, Valerio Nardone, Stefania Croci, Giuseppe Battaglia, Francesca Vanni, Cristiana Bellan, Marcella Barbarino, Veronica Ricci, Susan Costantini, Francesca Capone, Cirino Botta, Mayra Rachele Zarone, Gabriella Misso, Mariarosaria Boccellino, Michele Caraglia, Antonio Giordano, Piero Paladini, Pierfrancesco Tassone, Pierosandro Tagliaferri, Maria Grazia Cusi, Luigi Pirtoli, Pierpaolo Correale
Background: Results from the BEVA2007 trial, suggest that the metronomic chemotherapy regimen with dose-fractioned cisplatin and oral etoposide (mPE) +/- bevacizumab, a monoclonal antibody to the vascular endothelial growth factor (VEGF), shows anti-angiogenic and immunological effects and is a safe and active treatment for metastatic non-small cell lung cancer (mNSCLC) patients. We carried out a retrospective analysis aimed to evaluate the antitumor effects of this treatment in a subset of patients with squamous histology...
September 2017: Journal of Thoracic Disease
https://www.readbyqxmd.com/read/29221266/prognostic-impact-of-controlling-nutritional-status-score-in-resected-lung-squamous-cell-carcinoma
#16
Gouji Toyokawa, Yuka Kozuma, Taichi Matsubara, Naoki Haratake, Shinkichi Takamori, Takaki Akamine, Kazuki Takada, Masakazu Katsura, Mototsugu Shimokawa, Fumihiro Shoji, Tatsuro Okamoto, Yoshihiko Maehara
Background: The preoperative immune-nutritional status has been shown to predict the postoperative prognosis in various types of cancer; however, the prognostic significance of the controlling nutritional status (CONUT) score in resected lung squamous cell carcinoma (SCC) has yet to be elucidated. Methods: A total of 108 patients with resected lung SCC were analyzed for their clinicopathological factors, including the CONUT score, which can be calculated from the serum albumin, total cholesterol, and total peripheral lymphocyte count...
September 2017: Journal of Thoracic Disease
https://www.readbyqxmd.com/read/29217732/peptide-blocking-of-pd-1-pd-l1-interaction-for-cancer-immunotherapy
#17
Chunlin Li, Nengpan Zhang, Jundong Zhou, Chen Ding, Yaqing Jin, Xueyuan Cui, Kefeng Pu, Yimin Zhu
Immunotherapy has become a promising alternative therapeutic approach for cancer patients. Interruption of immune checkpoints, such as CTLA-4 and PD-1, has been verified to be a successful means for cancer therapy in clinical trials. Monoclonal antibody (mAb) targeting to PD-L1 has been approved to treat urothelial carcinoma, non-small cell lung cancer or merkel cell carcinoma by the Food and Drug Administration (FDA). However, the high cost of the antibody can limit its application. In our study, TPP-1 (targeting PD-L1 peptide), which specifically binds to PD-L1 with high affinity, was identified through bacterial surface display methods...
December 7, 2017: Cancer Immunology Research
https://www.readbyqxmd.com/read/29216787/mek-inhibitors-under-development-for-treatment-of-non-small-cell-lung-cancer
#18
Chul Kim, Giuseppe Giaccone
The mitogen-activated protein kinase (MAPK) pathway is intimately implicated in the molecular pathogenesis of non-small-cell lung cancer (NSCLC). Aberrant MAPK signaling resulting from the upstream activating mutations converges on mitogen-activated protein kinase kinase 1/2 (MEK1/2), making MEK inhibition an attractive strategy for the treatment of NSCLC. Several MEK inhibitors have demonstrated anticancer activity in patients with NSCLC. Areas covered: In this article, we discuss the biological rationale for the use of MEK inhibitors and summarize the clinical experience with MEK1/2 inhibitors for the treatment of NSCLC, from initial phase I studies to phase II/III studies, both as monotherapy or in combination with other anticancer agents...
December 7, 2017: Expert Opinion on Investigational Drugs
https://www.readbyqxmd.com/read/29213088/nsd1-inactivation-defines-an-immune-cold-dna-hypomethylated-subtype-in-squamous-cell-carcinoma
#19
Kevin Brennan, June Ho Shin, Joshua K Tay, Marcos Prunello, Andrew J Gentles, John B Sunwoo, Olivier Gevaert
Chromatin modifying enzymes are frequently mutated in cancer, resulting in widespread epigenetic deregulation. Recent reports indicate that inactivating mutations in the histone methyltransferase NSD1 define an intrinsic subtype of head and neck squamous cell carcinoma (HNSC) that features pronounced DNA hypomethylation. Here, we describe a similar hypomethylated subtype of lung squamous cell carcinoma (LUSC) that is enriched for both inactivating mutations and deletions in NSD1. The 'NSD1 subtypes' of HNSC and LUSC are highly correlated at the DNA methylation and gene expression levels, featuring ectopic expression of developmental transcription factors and genes that are also hypomethylated in Sotos syndrome, a congenital disorder caused by germline NSD1 mutations...
December 6, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29212506/chromosome-9p-copy-number-gains-involving-pd-l1-are-associated-with-a-specific-proliferation-and-immune-modulating-gene-expression-program-active-across-major-cancer-types
#20
Jan Budczies, Carsten Denkert, Balázs Győrffy, Peter Schirmacher, Albrecht Stenzinger
BACKGROUND: Inhibition of the PD-L1/PD-1 immune checkpoint axis represents one of the most promising approaches of immunotherapy for various cancer types. However, immune checkpoint inhibition is successful only in subpopulations of patients emphasizing the need for powerful biomarkers that adequately reflect the complex interaction between the tumor and the immune system. Recently, recurrent copy number gains (CNG) in chromosome 9p involving PD-L1 were detected in many cancer types including lung cancer, melanoma, bladder cancer, head and neck cancer, cervical cancer, soft tissue sarcoma, prostate cancer, gastric cancer, ovarian cancer, and triple-negative breast cancer...
December 6, 2017: BMC Medical Genomics
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