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https://www.readbyqxmd.com/read/29133939/precision-medicine-for-urothelial-bladder-cancer-update-on-tumour-genomics-and-immunotherapy
#1
REVIEW
Kenneth M Felsenstein, Dan Theodorescu
Effective management of advanced urothelial bladder cancer is challenging. New discoveries that improve our understanding of molecular bladder cancer subtypes have revealed numerous potentially targetable genomic alterations and demonstrated the efficacy of treatments that harness the immune system. These findings have begun to change paradigms of bladder cancer therapy. For example, DNA repair pathway mutations in genes such as ERCC2, FANCC, ATM, RB1, and others can predict responses to neoadjuvant platinum-based chemotherapies and to targeted therapies on the basis of mutation status...
November 14, 2017: Nature Reviews. Urology
https://www.readbyqxmd.com/read/29130342/nivolumab-in-recurrent-metastatic-head-and-neck-cancers
#2
Andy Karabajakian, Thibaut Reverdy, Max Gau, Jérôme Fayette
Head and neck cancer is an immunosuppressive disease, with a high proportion expressing PD-L1. Until recently, options were lacking in second line. Prognosis is poor especially for patients who progress during chemotherapy with survival often inferior to 6 months. Nivolumab is the only anti-PD1 agent to prolong survival in the second-line setting and is now the standard option since the CheckMate-141 trial. Treatment is generally well tolerated, patients seem to have a better quality of life when compared with chemotherapy...
November 13, 2017: Future Oncology
https://www.readbyqxmd.com/read/29127022/genetic-and-immune-profiles-of-solid-predominant-lung-adenocarcinoma-reveal-potential-immunotherapeutic-strategies
#3
Zhong-Yi Dong, Chao Zhang, Yu-Fa Li, Jian Su, Zhi Xie, Si-Yang Liu, Li-Xu Yan, Zhi-Hong Chen, Xue-Ning Yang, Jun-Tao Lin, Hai-Yan Tu, Jin-Ji Yang, Qing Zhou, Yue-Li Sun, Wen-Zhao Zhong, Yi-Long Wu
BACKGROUND: Subtype classification of lung adenocarcinoma (LUAD) divides different survivals and therapeutic vulnerabilities, while the underlying molecular mechanism is little to be known. This study sought to determine the genetic and immune profiles of histologic subtypes and identify the evidence for adjuvant immunotherapy. PATIENTS AND METHODS: We performed an integrated analysis on multidimensional data from a discovery set including cohorts of The Cancer Genome Atlas (TCGA) and the Broad set from the LUAD public database, and a validation set from the Guangdong Lung Cancer Institute (GLCI)...
November 7, 2017: Journal of Thoracic Oncology
https://www.readbyqxmd.com/read/29126088/in-the-immuno-oncology-era-is-anti-pd-1-or-anti-pd-l1-immunotherapy-modifying-the-sensitivity-to-conventional-cancer-therapies
#4
Sandrine Aspeslagh, Margarida Matias, Virginia Palomar, Laurent Dercle, Emilie Lanoy, Jean-Charles Soria, Sophie Postel-Vinay
INTRODUCTION: The advent of anti-programmed death receptor-1/ligand-1 antibodies (anti-PD(L)1) is profoundly changing the therapeutic strategy of oncology. As anti-PD(L)1 modulate tumour microenvironment, it might impact sensitivity to conventional cancer therapy (CCT). Therefore, we explored whether sensitivity to CCT was different before and after anti-PD(L)1 therapy. METHODS: Patients who started anti-PD(L)1 treatment at Gustave Roussy Cancer Centre between February 2012 and December 2015, and who received at least one line of CCT immediately before and immediately after anti-PD(L)1, were eligible...
November 7, 2017: European Journal of Cancer
https://www.readbyqxmd.com/read/29114543/molecular-mechanisms-of-programmed-cell-death-1-dependent-t-cell-suppression-relevance-for-immunotherapy
#5
REVIEW
Miren Zuazo, Maria Gato-Cañas, Noelia Llorente, María Ibañez-Vea, Hugo Arasanz, Grazyna Kochan, David Escors
Programmed cell death-1 (PD1) has become a significant target for cancer immunotherapy. PD1 and its receptor programmed cell death 1 ligand 1 (PDL1) are key regulatory physiological immune checkpoints that maintain self-tolerance in the organism by regulating the degree of activation of T and B cells amongst other immune cell types. However, cancer cells take advantage of these immunosuppressive regulatory mechanisms to escape T and B cell-mediated immunity. PD1 engagement on T cells by PDL1 on the surface of cancer cells dramatically interferes with T cell activation and the acquisition of effector capacities...
October 2017: Annals of Translational Medicine
https://www.readbyqxmd.com/read/29110262/mutational-diversity-of-lung-cancer-and-associated-lymph-nodes-an-exploratory-prospective-study-of-4-resected-ciiia-n2
#6
Antoine Legras, Hélène Roussel, Giuseppe Mangiameli, Alex Arame, Bertrand Grand, Ciprian Pricopi, Alain Badia, Laure Gibault, Cécile Badoual, Elizabeth Fabre, Pierre Laurent-Puig, Hélène Blons, Françoise Le Pimpec-Barthes
Mutational heterogeneity could explain different metastatic patterns among IIIA-N2 lung cancer and influence prognosis. The identification of subclonal mutations using deep sequencing to evaluate the degree of molecular heterogeneity may improve IIIA-N2 classification. The aim of this prospective study was to assess mutational and immunohistochemical characteristics in primary tumours and involved lymph nodes (LN) in operated patients. Four patients operated for primary lung carcinoma and unisite N2 mediastinal involvement were consecutively selected...
November 6, 2017: Pathology Oncology Research: POR
https://www.readbyqxmd.com/read/29096940/anti-pd1-pdl1-induced-psoriasis
#7
Dimitra Voudouri, Vasiliki Nikolaou, Konstantinos Laschos, Andriani Charpidou, Nikolaos Soupos, Ioanna Triantafyllopoulou, Ioanna Panoutsopoulou, Gerasimos Aravantinos, K Syrigos, A Stratigos
BACKGROUND: Immune checkpoint inhibitors are novel agents approved for the treatment of late-stage malignancies. Despite its important clinical benefits, checkpoint inhibition is associated with a unique spectrum of side effects known as immune-related adverse events. Skin toxicities are the most frequent immune-related adverse events during anti-PD1 blockade therapies. Among them, rare cases of psoriasis exacerbation have been reported. METHODS: We present the clinical characteristics of exacerbated psoriasis in 5 patients under anti-PD1/PDL1 therapy...
October 18, 2017: Current Problems in Cancer
https://www.readbyqxmd.com/read/29095280/primary-hypothyroidism-and-isolated-acth-deficiency-induced-by-nivolumab-therapy-case-report-and-review
#8
REVIEW
Mei Fang Zeng, Li Chen, Hong Ying Ye, Wei Gong, Li Nuo Zhou, Yi Ming Li, Xiao Long Zhao
RATIONALE: Nivolumab is a monoclonal IgG antibody blocking programmed death receptor-1 (PD1), leading to restoration of the natural T-cell-mediated immune response against the cancer cells. However, it also causes plenty of autoimmune-related adverse events, which often involves endocrine system. PATIENT CONCERNS: A 54-year-old male with renal clear cell carcinoma was treated with nivolumab intravenously. Routine monitoring showed elevated thyroid-stimulating hormone and low free thyroxine after the 6th administration of nivolumab...
November 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/29089645/identification-and-characterization-of-hla-a24-specific-xbp1-cd138-syndecan-1-and-cs1-slamf7-peptides-inducing-antigens-specific-memory-cytotoxic-t-lymphocytes-targeting-multiple-myeloma
#9
J Bae, T Hideshima, G L Zhang, J Zhou, D B Keskin, N C Munshi, K C Anderson
XBP1 (X-box binding protein 1), CD138 (Syndecan-1), and CS1 (SLAMF7) are highly expressed antigens in cancers including multiple myeloma (MM). Here we identify and characterize immunogenic HLA-A24 peptides derived from these antigens for potential vaccination therapy of HLA-A24+ patients with MM. The identified immunogenic HLA-A24-specific XBP1 unspliced (UN)185-193 (I S P W I L A V L), XBP1 spliced (SP)223-231 (V Y P E G P S S L), CD138265-273 (I F A V C L V G F) and CS1240-248 (L F V L G L F L W) peptides induced antigen-specific CTL with anti-MM activity in an HLA-A24 restricted manner...
November 1, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/29082853/cancer-gene-profiling-in-non-small-cell-lung-cancers-reveals-activating-mutations-in-jak2-and-jak3-with-therapeutic-implications
#10
Shuyu D Li, Meng Ma, Hui Li, Aneta Waluszko, Tatyana Sidorenko, Eric E Schadt, David Y Zhang, Rong Chen, Fei Ye
BACKGROUND: Next-generation sequencing (NGS) of cancer gene panels are widely applied to enable personalized cancer therapy and to identify novel oncogenic mutations. METHODS: We performed targeted NGS on 932 clinical cases of non-small-cell lung cancers (NSCLCs) using the Ion AmpliSeq™ Cancer Hotspot panel v2 assay. RESULTS: Actionable mutations were identified in 65% of the cases with available targeted therapeutic options, including 26% of the patients with mutations in National Comprehensive Cancer Network (NCCN) guideline genes...
October 30, 2017: Genome Medicine
https://www.readbyqxmd.com/read/29074426/survival-of-the-fittest-cancer-challenges-t-cell-metabolism
#11
Davide G Franchina, Feng He, Dirk Brenner
T cells represent the major contributors to antitumor-specific immunity among the tumor-infiltrating lymphocytes. However, tumors acquire ways to evade immunosurveillance and anti-tumor responses are too weak to eradicate the disease. T cells are often functionally impaired as a result of interaction with, or signals from, transformed cells and the tumor microenvironment, including stromal cells. Among these, nutrients use and consumption is critically important for the control of differentiation and effector mechanisms of T cells...
October 24, 2017: Cancer Letters
https://www.readbyqxmd.com/read/29069958/pd-l1-immunohistochemistry-for-non-small-cell-lung-carcinoma-which-strategy-should-be-adopted
#12
Paul Hofman
PD-L1 detection with immunohistochemistry (IHC) is the only predictive biomarker available to date for PD-L1/PD1 immunotherapy in thoracic oncology. While many studies have been published on this biomarker, they raise a number of questions concerning mainly, i) the type of antibody for use and its condition of utilization, ii) the threshold to be used, iii) the message and information to communicate to the thoracic oncologist and, iv) the adoption of this methodology as part of the daily practices of a pathology laboratory...
October 26, 2017: Expert Review of Molecular Diagnostics
https://www.readbyqxmd.com/read/29069740/blockage-of-foxp3-transcription-factor-dimerization-and-foxp3-aml1-interaction-inhibits-t-regulatory-cell-activity-sequence-optimization-of-a-peptide-inhibitor
#13
Teresa Lozano, Marta Gorraiz, Aritz Lasarte-Cía, Marta Ruiz, Obdulia Rabal, Julen Oyarzabal, Sandra Hervás-Stubbs, Diana Llopiz, Pablo Sarobe, Jesús Prieto, Noelia Casares, Juan José Lasarte
Although T regulatory cells (Treg) are essential for the prevention of autoimmune diseases, their immunoregulatory function restrains the induction of immune responses against cancer. Thus, development of inhibitors of FOXP3, a key transcription factor for the immunosuppressive activity of Treg, might give new therapeutic opportunities. In a previous work we identified a peptide (named P60) able to enter into the cells, bind to FOXP3, and impair Treg activity in vitro and in vivo. Here we show that P60 binds to the intermediate region of FOXP3 and inhibits its homodimerization as well as its interaction with the transcription factor AML1...
September 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/29061560/bitter-melon-prevents-the-development-of-4-nqo-induced-oral-squamous-cell-carcinoma-in-an-immunocompetent-mouse-model-by-modulating-immune-signalling
#14
Ratna B Ray, Subhayan Sur, Robert Steele, Rajeev Aurora, Mark Vavares, Katherine E Schwetye
Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer worldwide, and tobacco is one of the most common factors for HNSCC of the oral cavity. We have previously observed that bitter melon (Momordica charantia) extract (BME) exerts anti-proliferative activity against several cancers including HNSCC. In this study, we investigated the preventive role of BME in 4-nitroquinoline 1-oxide (4-NQO) carcinogen-induced HNSCC. We observed that BME feeding significantly reduced the incidence of 4-NQO induced oral cancer in a mouse model...
October 23, 2017: Cancer Prevention Research
https://www.readbyqxmd.com/read/29059149/targeting-immunosuppressive-adenosine-in-cancer
#15
REVIEW
Dipti Vijayan, Arabella Young, Michele W L Teng, Mark J Smyth
Despite the success of anti-programmed cell death protein 1 (PD1), anti-PD1 ligand 1 (PDL1) and anti-cytotoxic T lymphocyte antigen 4 (CTLA4) therapies in advanced cancer, a considerable proportion of patients remain unresponsive to these treatments (known as innate resistance). In addition, one-third of patients relapse after initial response (known as adaptive resistance), which suggests that multiple non-redundant immunosuppressive mechanisms coexist within the tumour microenvironment. A major immunosuppressive mechanism is the adenosinergic pathway, which now represents an attractive new therapeutic target for cancer therapy...
October 23, 2017: Nature Reviews. Cancer
https://www.readbyqxmd.com/read/29047105/%C3%AE-secretase-inhibitor-reduces-immunosuppressive-cells-and-enhances-tumour-immunity-in-head-and-neck-squamous-cell-carcinoma
#16
Liang Mao, Zhi-Li Zhao, Guang-Tao Yu, Lei Wu, Wei-Wei Deng, Yi-Cun Li, Jian-Feng Liu, Lin-Lin Bu, Bing Liu, Ashok B Kulkarni, Wen-Feng Zhang, Lu Zhang, Zhi-Jun Sun
Immune evasion is a hallmark feature of cancer, and it plays an important role in tumour initiation and progression. In addition, tumour immune evasion severely hampers the desired antitumour effect in multiple cancers. In this study, we aimed to investigate the role of the Notch pathway in immune evasion in the head and neck squamous cell carcinoma (HNSCC) microenvironment. We first demonstrated that Notch1 signalling was activated in a Tgfbr1/Pten-knockout HNSCC mouse model. Notch signalling inhibition using a γ-secretase inhibitor (GSI-IX, DAPT) decreased tumour burden in the mouse model after prophylactic treatment...
October 19, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/29045514/exploratory-analysis-of-the-association-of-depth-of-response-and-survival-in-patients-with-metastatic-non-small-cell-lung-cancer-treated-with-a-targeted-therapy-or-immunotherapy
#17
C E McCoach, G M Blumenthal, L Zhang, A Myers, S Tang, R Sridhara, P Keegan, R Pazdur, R C Doebele, D Kazandjian
Background: Response Evaluation Criteria in Solid Tumors (RECIST) permits rapid evaluation of new therapeutic strategies in cancer. However, RECIST does not capture the heterogeneity of response in highly active therapies. Depth of tumor response may provide a more granular view of response. We explored the association between, depth of response (DepOR), with overall survival (OS) and progression-free survival (PFS) for patients with NSCLC being treated with an ALK inhibitor (ALKi) or an anti-PD-1 antibody (Ab)...
November 1, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/29043842/the-protective-and-immunomodulatory-effects-of-fucoidan-against-7-12-dimethyl-benz-a-anthracene-induced-experimental-mammary-carcinogenesis-through-the-pd1-pdl1-signaling-pathway-in-rats
#18
Meilan Xue, Hui Liang, Qingjuan Tang, Chuanxing Xue, Xinjia He, Li Zhang, Zheng Zhang, Zhengyan Liang, Kang Bian, Lichen Zhang, Zhuxin Li
Fucoidan is a sulfated polysaccharide that is extracted from brown algae seaweed. This study was designed to evaluate the protective and immunomodulatory effects of dietary fucoidan on 7,12-dimethyl benz[a]anthracene (DMBA)-induced experimental mammary carcinogenesis in rats. Sixty Sprague-Dawley rats were randomly assigned to four equal groups: the control group (control group), the cancer model group (model group), and the F1 and F2 groups, which were fed fucoidan at concentrations of 200 and 400 mg/kg·body weight, respectively...
October 18, 2017: Nutrition and Cancer
https://www.readbyqxmd.com/read/29016938/preclinical-investigation-of-gene-mediated-cytotoxic-immunotherapy-and-checkpoint-blockade-in-glioblastoma
#19
Maria-Carmela Speranza, Carmela Passaro, Franz Ricklefs, Kazue Kasai, Sarah R Klein, Hiroshi Nakashima, Johanna K Kaufmann, Abdul-Kareem Ahmed, Michal O Nowicki, Prisca Obi, Agnieszka Bronisz, Estuardo Aguilar-Cordova, Laura K Aguilar, Brian W Guzik, Xandra Breakefield, Ralph Weissleder, Gordon J Freeman, David A Reardon, Patrick Wen, E Antonio Chiocca, Sean E Lawler
Background: Combined immunotherapy approaches are promising cancer treatments. We evaluated anti-PD-1 treatment combined with Gene-mediated cytotoxic immunotherapy (GMCI) performed by intratumoral injection of a prodrug metabolizing non-replicating adenovirus (AdV-tk), providing insitu chemotherapy and immune stimulation. Methods: The effects of GMCI on PD-L1 expression in glioblastoma were investigated in vitro and in vivo. The efficacy of the combination was investigated in two syngeneic mouse glioblastoma models (GL261 and CT-2A)...
July 24, 2017: Neuro-oncology
https://www.readbyqxmd.com/read/29016555/interleukin-10-regulated-tumour-tolerance-in-non-small-cell-lung-cancer
#20
Julius Malte Vahl, Juliane Friedrich, Susanne Mittler, Sonja Trump, Lisanne Heim, Katerina Kachler, Liubov Balabko, Nicole Fuhrich, Carol-Immanuel Geppert, Denis Iulian Trufa, Nina Sopel, Ralf Rieker, Horia Sirbu, Susetta Finotto
BACKGROUND: Lung cancer is the most life-threatening cancer type worldwide. Treatment options include surgery, radio- and chemotherapy, as well as the use of immunomodulatory antibodies. Interleukin (IL)-10 is an immunosuppressive cytokine involved in tumour immune escape. METHODS: Immunohistochemistry (IHC) on human lung surgery tissue as well as human tumour cell line cultures, FACS analysis, real-time PCR and experimental lung cancer. RESULTS: Here we discovered a positive correlation between IL-10 and IL-10 receptor (IL-10R) expression in the lung with tumour diameter in patients with lung cancer (non-small cell lung cancer), the most life-threatening cancer type worldwide...
October 10, 2017: British Journal of Cancer
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