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immunotherapy of cancer

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https://www.readbyqxmd.com/read/29161279/whole-exome-sequencing-for-determination-of-tumor-mutation-load-in-liquid-biopsy-from-advanced-cancer-patients
#1
Florence Koeppel, Steven Blanchard, Cécile Jovelet, Bérengère Genin, Charles Marcaillou, Emmanuel Martin, Etienne Rouleau, Eric Solary, Jean-Charles Soria, Fabrice André, Ludovic Lacroix
Tumor mutation load (TML) has been proposed as a biomarker of patient response to immunotherapy in several studies. TML is usually determined by tumor biopsy DNA (tDNA) whole exome sequencing (WES), therefore TML evaluation is limited by informative biopsy availability. Circulating cell free DNA (cfDNA) provided by liquid biopsy is a surrogate specimen to biopsy for molecular profiling. Nevertheless performing WES on DNA from plasma is technically challenging and the ability to determine tumor mutation load from liquid biopsies remains to be demonstrated...
2017: PloS One
https://www.readbyqxmd.com/read/29160310/cyclin-d-cdk4-kinase-destabilizes-pd-l1-via-cul3-spop-to-control-cancer-immune-surveillance
#2
Jinfang Zhang, Xia Bu, Haizhen Wang, Yasheng Zhu, Yan Geng, Naoe Taira Nihira, Yuyong Tan, Yanpeng Ci, Fei Wu, Xiangpeng Dai, Jianping Guo, Yu-Han Huang, Caoqi Fan, Shancheng Ren, Yinghao Sun, Gordon J Freeman, Piotr Sicinski, Wenyi Wei
Treatments that target immune checkpoints, such as the one mediated by programmed cell death protein 1 (PD-1) and its ligand PD-L1, have been approved for treating human cancers with durable clinical benefit(1,2). However, many cancer patients fail to respond to anti-PD-1/PD-L1 treatment, and the underlying mechanism(s) is not well understood(3-5). Recent studies revealed that response to PD-1/PD-L1 blockade might correlate with PD-L1 expression levels in tumor cells(6,7). Hence, it is important to mechanistically understand the pathways controlling PD-L1 protein expression and stability, which can offer a molecular basis to improve the clinical response rate and efficacy of PD-1/PD-L1 blockade in cancer patients...
November 16, 2017: Nature
https://www.readbyqxmd.com/read/29159802/adenovirus-vector-based-prime-boost-vaccination-via-heterologous-routes-induces-cervicovaginal-cd8-t-cell-responses-against-hpv16-oncoproteins
#3
Nicolas Çuburu, Selina Khan, Cynthia D Thompson, Rina Kim, Jort Vellinga, Roland Zahn, Douglas R Lowy, Gert Scheper, John T Schiller
Recent advances in immunotherapy against cancer underscore the importance of T lymphocytes and tumor microenvironment, but few vaccines targeting cancer have been approved likely due in part to the dearth of common tumor antigens, insufficient immunogenicity and the evolution of immune evasion mechanisms during the progression to malignancy. Human papillomaviruses (HPV) are the primary etiologic agents of cervical cancer and progression from persistent HPV-infection to cervical intraepithelial lesions and eventually cancer requires persistent expression of the oncoproteins E6 and E7...
November 21, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/29159792/seom-clinical-guidelines-for-the-treatment-of-head-and-neck-cancer-2017
#4
L C Iglesias Docampo, V Arrazubi Arrula, N Baste Rotllan, A Carral Maseda, B Cirauqui Cirauqui, Y Escobar, J J Lambea Sorrosal, M Pastor Borgoñón, A Rueda, J J Cruz Hernández
Head and neck cancer (HNC) is defined as malignant tumours located in the upper aerodigestive tract and represents 5% of oncologic cases in adults in Spain. More than 90% of these tumours have squamous histology. In an effort to incorporate evidence obtained since 2013 publication, Spanish Society of Medical Oncology (SEOM) presents an update of HNC diagnosis and treatment guideline. The eighth edition of TNM classification, published in January 2017, introduces important changes for p16-positive oropharyngeal tumours, for lip and oral cavity cancer and for N3 category...
November 20, 2017: Clinical & Translational Oncology
https://www.readbyqxmd.com/read/29159766/incidence-of-immune-related-adverse-events-and-its-association-with-treatment-outcomes-the-md-anderson-cancer-center-experience
#5
Takeo Fujii, Rivka R Colen, Mehmet Asim Bilen, Kenneth R Hess, Joud Hajjar, Maria E Suarez-Almazor, Anas Alshawa, David S Hong, Apostolia Tsimberidou, Filip Janku, Jing Gong, Bettzy Stephen, Vivek Subbiah, Sarina A Piha-Paul, Siqing Fu, Padmanee Sharma, Tito Mendoza, Anisha Patel, Selvi Thirumurthi, Ajay Sheshadri, Funda Meric-Bernstam, Aung Naing
Background Immunotherapy is emerging as the cornerstone for treatment of patients with advanced cancer, but significant toxicity (immune-related adverse events [irAEs]) associated with unbridled T cell activity remains a concern. Patients and methods A retrospective review of the electronic medical records of 290 patients with advanced cancer treated on an immunotherapy-based clinical trial in the Department of Investigational Cancer Therapeutics at The University of Texas MD Anderson Cancer Center between February 2010 and September 2015 was performed...
November 21, 2017: Investigational New Drugs
https://www.readbyqxmd.com/read/29159318/young-donor-white-blood-cell-immunotherapy-induces-extensive-tumor-necrosis-in-advanced-stage-solid-tumors
#6
Dipnarine Maharaj, Pedro G Vianna, Wendy Ward, Anthony J Messina, Trevor Rayborn, Jacqueline V Gouvea, Richard D Hammer, Zheng Cui
Background: In the past decade, a variety of immunotherapy approaches focused predominantly on the adaptive immune system have shown unprecedented responses in patients with advanced-stage malignancies. However, studies in spontaneous regression/complete resistance (SR/CR) mice and humans have shown a novel innate cancer-killing activity mediated by granulocytes, which is completely transferable for prevention or therapy against established malignancies. Methods: Three patients with advanced, relapsed or refractory solid tumors for which no standard therapy was available or was refused were enrolled into this ongoing combined phase I/II open label clinical trial testing the safety, dose tolerance, and possible antineoplastic efficacy of sequential infusions of HLA-mismatched non-irradiated allogeneic white cells (68-91% granulocytes) collected by leukapheresis from young, healthy donors (age 18-35) following mobilization with granulocyte colony stimulating factor (G-CSF) and dexamethasone...
October 2017: Heliyon
https://www.readbyqxmd.com/read/29159146/lactobacillus-plantarum-induces-apoptosis-in-oral-cancer-kb-cells-through-upregulation-of-pten-and-downregulation-of-mapk-signalling-pathways
#7
Abbas Asoudeh-Fard, Abolfazl Barzegari, Alireza Dehnad, Sepideh Bastani, Asal Golchin, Yadollah Omidi
Introduction: The oral tumor is the sixth most prevalent type of cancer worldwide and the second leading cause of cancer-related mortality. Although chemotherapy and immunotherapy are the main strategies for the treatment of oral cancer, an emergence of inevitable resistance to these treatment modalities is the major drawback that causes recurrence of the disease. Nowadays, probiotics have been suggested as adjunctive and complementary treatment modalities for improving the impacts of chemotherapy and immunotherapy agents...
2017: BioImpacts: BI
https://www.readbyqxmd.com/read/29158834/rational-design-of-polymeric-hybrid-micelles-to-overcome-lymphatic-and-intracellular-delivery-barriers-in-cancer-immunotherapy
#8
Hanmei Li, Yanping Li, Xue Wang, Yingying Hou, Xiaoyu Hong, Tao Gong, Zhirong Zhang, Xun Sun
Poor distribution of antigen/adjuvant to target sites and inadequate induction of T cell responses remain major challenges in cancer immunotherapy because of the lack of appropriate delivery systems. Nanocarrier-based antigen delivery systems have emerged as an innovative strategy to improve vaccine efficacy. Here we present polymeric hybrid micelles (PHMs) as a simple and potent antigen/adjuvant co-delivery system with highly tunable properties. PHMs consist of two amphiphilic diblock copolymers, polycaprolactone-polyethylenimine (PCL-PEI) and polycaprolactone-polyethyleneglycol (PCL-PEG)...
2017: Theranostics
https://www.readbyqxmd.com/read/29158797/pd-l1-is-a-prognostic-biomarker-in-resected-nsclc-patients-with-moderate-high-smoking-history-and-elevated-serum-scca-level
#9
Lianjing Cao, Xinyue Wang, Shouying Li, Qiongjie Zhi, Yuqian Wang, Liuchun Wang, Kai Li, Richeng Jiang
Programmed cell death-1 (PD-1) -targeted immunotherapy has become a promising treatment paradigm for patients with advanced non-small cell lung cancer (NSCLC). Clinical responses to checkpoint inhibition therapy in NSCLC have been associated with programmed death-1 ligand 1 (PD-L1) expression. However, the association between the expression of PD-L1 and PD-L2 and the clinicopathological features and patient outcomes in NSCLC remain unclear. We retrospectively analyzed 364 patients (158 squamous cell carcinoma and 206 adenocarcinoma) who underwent complete resection between 2009 and 2012...
2017: Journal of Cancer
https://www.readbyqxmd.com/read/29158791/correlation-of-cancer-stem-cell-markers-and-immune-cell-markers-in-resected-non-small-cell-lung-cancer
#10
Zhaoqin Huang, Haining Yu, Jianbo Zhang, Haiyan Jing, Wanqi Zhu, Xiaolin Li, Lingling Kong, Ligang Xing, Jinming Yu, Xiangjiao Meng
Background: Recent studies confirmed that immunotherapy showed prominent efficacy in non-small cell lung cancer (NSCLC). Cancer stem cells/cancer initiating cells are resistant to anticancer treatment. The purpose of the study was to analyze the correlation of cancer stem cells/cancer initiating cells and tumor-infiltrating immune cells in NSCLC. Methods: CD133, octamer 4 (OCT-4), CD8, CD56, human leukocyte antigen (HLA) class I and programmed death ligand-1 (PD-L1) were assessed in 172 resected NSCLC samples...
2017: Journal of Cancer
https://www.readbyqxmd.com/read/29158788/programmed-death-ligand-1-pd-l1-expression-in-primary-angiosarcoma
#11
Gerardo Botti, Giosuè Scognamiglio, Laura Marra, Antonio Pizzolorusso, Maurizio Di Bonito, Rossella De Cecio, Monica Cantile, Annarosaria De Chiara
Angiosarcomas are rare malignant endothelial-cell tumors of vascular or lymphatic origin, and are among the most aggressive subtypes of soft-tissue sarcomas. The prognosis is poor and treatment is challenging in many cases. PD-1/PD-L1 pathway plays a critical role in immune escape of tumor cells. Recent studies described that PD-L1 is widely expressed in various types of cancer, providing the basis for the development of PD1/PD-L1 antibodies as anti-cancer immunotherapy. Despite the well-known potential of PD-L1 as prognostic and predictive biomarker, only few studies described its IHC expression in cancer subtypes for the extreme difficulty in developing standard protocol with the different antibody clones available...
2017: Journal of Cancer
https://www.readbyqxmd.com/read/29158380/anti-sirp%C3%AE-antibody-immunotherapy-enhances-neutrophil-and-macrophage-antitumor-activity
#12
Nan Guo Ring, Dietmar Herndler-Brandstetter, Kipp Weiskopf, Liang Shan, Jens-Peter Volkmer, Benson M George, Melanie Lietzenmayer, Kelly M McKenna, Tejaswitha J Naik, Aaron McCarty, Yunjiang Zheng, Aaron M Ring, Richard A Flavell, Irving L Weissman
Cancer immunotherapy has emerged as a promising therapeutic intervention. However, complete and durable responses are only seen in a fraction of patients who have cancer. A key factor that limits therapeutic success is the infiltration of tumors by cells of the myeloid lineage. The inhibitory receptor signal regulatory protein-α (SIRPα) is a myeloid-specific immune checkpoint that engages the "don't eat me" signal CD47 expressed on tumors and normal tissues. We therefore developed the monoclonal antibody KWAR23, which binds human SIRPα with high affinity and disrupts its binding to CD47...
November 20, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29158230/neoantigen-quality-predicts-immune-response-survival
#13
(no author information available yet)
A new mathematical model finds that tumor neoantigen quality trumps quantity when it comes to predicting response to immunotherapy and the likelihood of long-term survival among patients with cancer.
November 20, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/29158137/recent-developments-in-the-management-of-bladder-cancer-introduction
#14
REVIEW
Angela B Smith
An upsurge of advances in the management of bladder cancer has rapidly occurred over the past 2 years. In this issue, recent developments in the management of bladder cancer will be discussed, including the emerging role of immunotherapy, biomarkers, and advanced imaging.
November 17, 2017: Urologic Oncology
https://www.readbyqxmd.com/read/29157965/polymer-based-nanoparticles-loaded-with-a-tlr7-ligand-to-target-the-lymph-node-for-immunostimulation
#15
Jérôme Widmer, Cédric Thauvin, Inès Mottas, Van N'guyen, Florence Delie, Eric Allémann, Carole Bourquin
Small-molecule agonists for the Toll-like receptors (TLR) 7 and 8 are effective for the immunotherapy of skin cancer when used as topical agents. Their systemic use has however been largely unsuccessful due to dose-limiting toxicity. We propose a polymer-based nanodelivery system to target resiquimod, a TLR7 ligand, to the lymph node in order to focus the immunostimulatory activity and to prevent a generalized inflammatory response. We demonstrate successful encapsulation of resiquimod in methoxypoly(ethylene glycol)-b-poly(DL-lactic acid) (mPEG-PLA) and mixed poly(DL-lactic-co-glycolic acid) (PLGA)/mPEG-PLA nanoparticles...
November 17, 2017: International Journal of Pharmaceutics
https://www.readbyqxmd.com/read/29157828/immune-related-and-adverse-drug-reactions-to-low-versus-high-initial-doses-of-viscum-album-l-in-cancer-patients
#16
Friedemann Schad, Anja Thronicke, Antje Merkle, Harald Matthes, Megan L Steele
BACKGROUND: Immune-related adverse drug reactions (ADRs) to immunotherapy agents have been associated with beneficial clinical outcomes in oncology. Viscum album L. (VA, European mistletoe) is frequently used as an immunomodulatory agent alongside conventional cancer treatment in Europe. VA has been associated with improved quality of life and a reduction in chemotherapy-related ADRs. Beneficial effects of VA are believed to be related to its immunomodulatory properties. Current guidelines recommend commencing with a low dose and increasing slowly overtime, however, off-label prescribing of high initial doses is common...
December 1, 2017: Phytomedicine: International Journal of Phytotherapy and Phytopharmacology
https://www.readbyqxmd.com/read/29157306/a-pilot-study-of-the-immunogenicity-of-a-9-peptide-breast-cancer-vaccine-plus-poly-iclc-in-early-stage-breast-cancer
#17
Patrick M Dillon, Gina R Petroni, Mark E Smolkin, David R Brenin, Kimberly A Chianese-Bullock, Kelly T Smith, Walter C Olson, Ibrahim S Fanous, Carmel J Nail, Christiana M Brenin, Emily H Hall, Craig L Slingluff
BACKGROUND: Breast cancer remains a leading cause of cancer death worldwide. There is evidence that immunotherapy may play a role in the eradication of residual disease. Peptide vaccines for immunotherapy are capable of durable immune memory, but vaccines alone have shown sparse clinical activity against breast cancer to date. Toll-like receptor (TLR) agonists and helper peptides are excellent adjuvants for vaccine immunotherapy and they are examined in this human clinical trial. METHODS: A vaccine consisting of 9 MHC class I-restricted breast cancer-associated peptides (from MAGE-A1, -A3, and -A10, CEA, NY-ESO-1, and HER2 proteins) was combined with a TLR3 agonist, poly-ICLC, along with a helper peptide derived from tetanus toxoid...
November 21, 2017: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/29157298/impressive-response-to-immunotherapy-in-a-metastatic-gastric-cancer-patient-could-somatic-copy-number-alterations-help-patient-selection
#18
Gustavo Dos Santos Fernandes, Daniel da Motta Girardi, Luiza Dib Batista Bugiato Faria, João Paulo Giacomini Bernardes, Renata de Almeida Coudry
BACKGROUND: Metastatic gastric cancer (GC) is an incurable and aggressive disease with a poor prognosis. Immunotherapy is an attractive approach for treating patients with cancer, and studies using immunotherapy have shown promising results in melanoma, kidney and non-small cell lung cancers, among others. CASE PRESENTATION: We present a case of a 50-year-old woman with metastatic GC whose cancer had progressed after first-line chemotherapy and who received pembrolizumab as an experimental treatment...
November 21, 2017: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/29157296/biomarkers-for-immunotherapy-in-bladder-cancer-a-moving-target
#19
REVIEW
David H Aggen, Charles G Drake
Treatment options for metastatic urothelial carcinoma (mUC) remained relative unchanged over the last 30 years with combination chemotherapy as the mainstay of treatment. Within the last year the landscape for mUC has seismically shifted following the approval of five therapies targeting the programmed cell death protein (PD-1)/programmed cell death ligand 1 (PD-L1) axis. Notably, the anti-PD-1 antibody pembrolizumab demonstrated improved OS relative to chemotherapy in a randomized phase III study for second line treatment of mUC; this level 1 evidence led to approval from the U...
November 21, 2017: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/29157287/safety-in-treatment-of-hepatocellular-carcinoma-with-immune-checkpoint-inhibitors-as-compared-to-melanoma-and-non-small-cell-lung-cancer
#20
Zachary J Brown, Bernd Heinrich, Seth M Steinberg, Su Jong Yu, Tim F Greten
BACKGROUND: Hepatocellular carcinoma (HCC) is a major health problem worldwide with increasing incidence rates. As HCC traditionally occurs in chronically inflamed livers, this inflammation aids to drive oncogenesis and often renders these lesions to be immunogenic and therefore potential targets for immunotherapy. As patients with HCC generally have underlying liver dysfunction, we sought to determine if immune checkpoint inhibitors were safe to use in patients with HCC as compared to melanoma and non-small cell lung cancer (NSCLC) in terms of the gastrointestinal side effects of elevation of aspartate aminotransferase (AST), alanine aminotransferase (ALT), and diarrhea as well as patients who drop out of the study due to drug toxicity and death secondary to drug toxicity...
November 21, 2017: Journal for Immunotherapy of Cancer
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