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https://www.readbyqxmd.com/read/29667757/successful-treatment-with-nivolumab-for-lung-cancer-with-low-expression-of-pd-l1-and-prominent-tumor-infiltrating-b-cells-and-immunoglobulin-g
#1
Takayuki Suyama, Yuichi Fukuda, Hiroshi Soda, Daiki Ogawara, Keisuke Iwasaki, Takuya Hara, Masataka Yoshida, Tatsuhiko Harada, Asuka Umemura, Hiroyuki Yamaguchi, Hiroshi Mukae
Little is known about the anti-tumor activity of humoral immunity in lung cancer patients treated with nivolumab, an immune checkpoint inhibitor. Herein, we report a case of lung cancer with 5% expression of PD-L1, in which a partial response to nivolumab was sustained for > 7 months. Immunohistochemical analysis of the metastatic lymph node biopsy specimen showed prominent accumulation of plasma cells and immunoglobulin G. These findings suggest that pre-existing humoral immunity may be worth considering as a candidate therapeutic biomarker of nivolumab in some lung cancer patients...
April 18, 2018: Thoracic Cancer
https://www.readbyqxmd.com/read/29667169/expression-of-scavenger-receptor-marco-defines-a-targetable-tumor-associated-macrophage-subset-in-non-small-cell-lung-cancer
#2
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
#3
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
#4
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/29666465/molecular-epidemiology-of-lung-cancer-in-iran-implications-for-drug-development-and-cancer-prevention
#5
REVIEW
Zahra Fathi, Nicholas L Syn, Jian-Guo Zhou, Raheleh Roudi
Epidemiological studies undertaken over the past decades reveal a gradual but progressive increase in the incidence and mortality attributable to lung cancer in the Islamic Republic of Iran, a sovereign state geographically situated at the crossroads of Central Eurasia and Western Asia. We identified references published in English and Persian through searches of PubMed, EMBASE, Web of Science, Scopus, and the Scientific Information Database (SID)-a specialized Iranian database, which indexes Iranian scientific journals-between inception and 15 September 2017...
April 18, 2018: Journal of Human Genetics
https://www.readbyqxmd.com/read/29666298/delayed-autoimmune-toxicity-occurring-several-months-after-cessation-of-anti-pd-1-therapy
#6
Sagun Parakh, Jonathan Cebon, Oliver Klein
Treatment with anti-programmed cell death protein 1 (PD-1) antibodies has demonstrated clinical efficacy in a whole range of malignancies including advanced melanoma, renal cell cancer, bladder cancer, and non-small cell lung cancer. Immune-related adverse events are a unique side effect of checkpoint regulator therapy including anti-PD-1 antibodies. Treatment-related autoimmunity can occur in any organ system, with the median onset usually within 5-15 weeks from the commencement of therapy, depending on the organ system involved...
April 17, 2018: Oncologist
https://www.readbyqxmd.com/read/29663879/anti-cancer-effects-of-metformin-recent-evidences-for-its-role-in-prevention-and-treatment-of-cancer
#7
Masoumeh Kheirandish, Hamidreza Mahboobi, Maryam Yazdanparast, Warda Kamal, Mohammad A Kamal
Metformin is widely used for the management of type 2 diabetes mellitus (T2DM). Recently growing evidence has shown its anti-cancer effects. The results are mainly obtained from observational studies and thus, little information is available concerning the mechanisms of action. Adenosine monophosphate (AMP)-activated protein kinase (AMPK) plays an important role in the mechanism of action of metformin. The anti-cancer mechanisms of metformin include direct and indirect effects. The direct effects of metformin include AMPK-independent and AMPK-dependent effects, whereas the decrease in glucose level, hyperinsulinemia, and Insulin-like growth factor 1 (IGF-1) level was considered its indirect effects...
April 16, 2018: Current Drug Metabolism
https://www.readbyqxmd.com/read/29663630/from-humans-to-hydra-patterns-of-cancer-across-the-tree-of-life
#8
Thales A F Albuquerque, Luisa Drummond do Val, Aoife Doherty, João Pedro de Magalhães
Cancer is a disease of multicellularity; it originates when cells become dysregulated due to mutations and grow out of control, invading other tissues and provoking discomfort, disability, and eventually death. Human life expectancy has greatly increased in the last two centuries, and consequently so has the incidence of cancer. However, how cancer patterns in humans compare to those of other species remains largely unknown. In this review, we search for clues about cancer and its evolutionary underpinnings across the tree of life...
April 16, 2018: Biological Reviews of the Cambridge Philosophical Society
https://www.readbyqxmd.com/read/29663282/the-frozen-brain-state-of-cryptococcus-gattii-a-globe-trotting-tropical-neurotropic-fungus
#9
Paul T Akins, Brian Jian
Initially reported in tropical regions, Cryptococcus gattii infection is now diagnosed globally. METHODS: case report; Literature review. Although initial reports described outbreaks of pulmonary and central nervous system (CNS) disease in tropical regions such as Australia and New Guinea, it is now clear that Cryptococcus gattii is a global, neurotropic pathogen. In contrast with C. neoformans, C. gattii patients are more likely to present with cryptococcomas in the brain and lungs and are often HIV negative...
April 16, 2018: Neurocritical Care
https://www.readbyqxmd.com/read/29662663/impact-of-antibiotic-treatment-on-immune-checkpoint-blockade-efficacy-in-advanced-non-squamous-non-small-cell-lung-cancer
#10
Florian Huemer, Gabriel Rinnerthaler, Theresa Westphal, Hubert Hackl, Georg Hutarew, Simon Peter Gampenrieder, Lukas Weiss, Richard Greil
Introduction: Despite durable responses from immune-checkpoint blockade (ICB) in a subset of patients with advanced non-small cell lung cancer (NSCLC), the majority of patients do not derive benefit from this treatment. In this analysis we evaluated the impact of concomitant administration of antibiotics during initiation of ICB on clinical outcome. Methods: Advanced non-squamous NSCLC patients receiving ICB as second- or later line between 2015 and 2017 at our tertiary cancer center in Salzburg (Austria) were included...
March 27, 2018: Oncotarget
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/29662483/long-non-coding-rna-hoxa-transcript-antisense-rna-myeloid-specific-1-hoxa1-axis-downregulates-the-immunosuppressive-activity-of-myeloid-derived-suppressor-cells-in-lung-cancer
#13
Xinyu Tian, Jie Ma, Ting Wang, Jie Tian, Yue Zhang, Lingxiang Mao, Huaxi Xu, Shengjun Wang
HOXA transcript antisense RNA myeloid-specific 1 (HOTAIRM1) is a long non-coding RNA that has been shown to be a key regulator of myeloid cell development by targeting HOXA1. Myeloid-derived suppressor cells (MDSCs) are a heterogeneous population of immature myeloid cells that possess immunosuppressive function. However, the impact of HOTAIRM1 on the development of MDSCs remains unknown. In this study, we demonstrated that HOTAIRM1 was expressed in MDSCs and that overexpression of HOTAIRM1 could downregulate the expression of suppressive molecules in MDSCs...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29661145/therapeutic-cancer-vaccine-phase-i-clinical-tolerance-study-of-hu-rhegf-rp64k-mont-in-patients-with-newly-diagnosed-advanced-non-small-cell-lung-cancer
#14
Puyuan Xing, Hongyu Wang, Sheng Yang, Xiaohong Han, Yan Sun, Yuankai Shi
BACKGROUND: Hu-rhEGF-rP64k/Mont is a biotechnology product for the treatment of advanced non-small cell lung cancer (NSCLC). The vaccine induces a neutralizing antibody-mediated immune response, against the normal circulating self-protein antigen epidermal growth factor (EGF), which prevents its binding to and activation of the EGF receptor, inhibiting the transduction of the signals that drive cancer cell proliferation, survival and spread. This phase I study aimed to evaluate the safety and the immunological response of Hu-rhEGF-rP64k vaccine in NSCLC patients...
April 16, 2018: BMC Immunology
https://www.readbyqxmd.com/read/29659925/tobacco-smoking-associated-alterations-in-the-immune-microenvironment-of-squamous-cell-carcinomas
#15
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
#16
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/29657128/genomic-features-of-response-to-combination-immunotherapy-in-patients-with-advanced-non-small-cell-lung-cancer
#17
Matthew D Hellmann, Tavi Nathanson, Hira Rizvi, Benjamin C Creelan, Francisco Sanchez-Vega, Arun Ahuja, Ai Ni, Jacki B Novik, Levi M B Mangarin, Mohsen Abu-Akeel, Cailian Liu, Jennifer L Sauter, Natasha Rekhtman, Eliza Chang, Margaret K Callahan, Jamie E Chaft, Martin H Voss, Megan Tenet, Xue-Mei Li, Kelly Covello, Andrea Renninger, Patrik Vitazka, William J Geese, Hossein Borghaei, Charles M Rudin, Scott J Antonia, Charles Swanton, Jeff Hammerbacher, Taha Merghoub, Nicholas McGranahan, Alexandra Snyder, Jedd D Wolchok
Combination immune checkpoint blockade has demonstrated promising benefit in lung cancer, but predictors of response to combination therapy are unknown. Using whole-exome sequencing to examine non-small-cell lung cancer (NSCLC) treated with PD-1 plus CTLA-4 blockade, we found that high tumor mutation burden (TMB) predicted improved objective response, durable benefit, and progression-free survival. TMB was independent of PD-L1 expression and the strongest feature associated with efficacy in multivariable analysis...
April 12, 2018: Cancer Cell
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
#18
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/29656749/tumor-associated-macrophages-support-the-growth-of-fgf9-induced-lung-adenocarcinoma-by-multiple-mechanisms
#19
Ahmed E Hegab, Mari Ozaki, Shizuko Kagawa, Junko Hamamoto, Hiroyuki Yasuda, Katsuhiko Naoki, Kenzo Soejima, Yongjun Yin, Tomonari Kinoshita, Tomonori Yaguchi, Yutaka Kawakami, David M Ornitz, Tomoko Betsuyaku
OBJECTIVES: Tumor-associated macrophages (TAMs) are known to promote tumorigenesis but the mechanism(s) remain elusive. We have developed a mouse model of lung cancer that is initiated through an inducible overexpression of fibroblast growth factor 9 (FGF9) in type-2 pneumocytes. Expression of FGF9 in adult lungs resulted in a rapid development of multiple adenocarcinoma-like tumor nodules, and is associated with an intense immunological reaction. The purpose of this study is to characterize the immune response to the FGF9-induced lung adenocarcinoma and to determine the contribution of TAMs to growth and survival of these tumors...
May 2018: Lung Cancer: Journal of the International Association for the Study of Lung Cancer
https://www.readbyqxmd.com/read/29656748/nivolumab-induced-severe-pancytopenia-in-a-patient-with-lung-adenocarcinoma
#20
Kentaro Tokumo, Takeshi Masuda, Takahiko Miyama, Shinichiro Miura, Kakuhiro Yamaguchi, Shinjiro Sakamoto, Yasushi Horimasu, Taku Nakashima, Shintaro Miyamoto, Takashi Yoshida, Hiroshi Iwamoto, Kazunori Fujitaka, Hironobu Hamada, Noboru Hattori
Severe leukopenia, thrombocytopenia, and bi-cytopenia due to nivolumab have been reported. In this report, we present the first case of nivolumab-induced severe pancytopenia in a patient with lung adenocarcinoma. A 56-year-old Japanese man with lung adenocarcinoma received nivolumab therapy as second-line treatment. After 3 cycles of this therapy, although computed tomography (CT) showed a reduced tumor size, laboratory findings revealed pancytopenia and a bone marrow biopsy showed a severely hypoplastic marrow...
May 2018: Lung Cancer: Journal of the International Association for the Study of Lung Cancer
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