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Immunotherapy

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https://www.readbyqxmd.com/read/29161564/cell-biology-when-your-own-chromosomes-act-like-foreign-dna
#1
Alexander Spektor, Neil T Umbreit, David Pellman
Two recent papers report the activation of a pro-inflammatory response by cytoplasmic DNA from aberrant nuclear structures called micronuclei. The findings have implications for tumor immunity, immunotherapy biomarker discovery, and possibly the many-sided effects of senescence-associated secretory phenotype.
November 20, 2017: Current Biology: CB
https://www.readbyqxmd.com/read/29161279/whole-exome-sequencing-for-determination-of-tumor-mutation-load-in-liquid-biopsy-from-advanced-cancer-patients
#2
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
#3
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/29159975/rcat-reflects-symptom-control-and-quality-of-life-in-allergic-rhinoconjunctivitis-patients
#4
J-P Liedtke, A Mandl, J Köther, J Chwieralski, K Shah-Hosseini, U Pieper-Fürst, S Allekotte, R Mösges
BACKGROUND: The Global Allergy and Asthma European Network (GA(2) LEN) Taskforce has requested more data on correlations between various Patient Reported Outcomes (PROs) in clinical trials on allergy. We compared three tools-the Rhinitis Control Assessment Test (RCAT), Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ), and Rhinitis Total Symptom Score (RTSS)-to determine whether the RCAT alone is a sufficient primary outcome parameter in clinical trials on allergic rhinoconjunctivitis...
November 21, 2017: Allergy
https://www.readbyqxmd.com/read/29159964/blocking-antibodies-induced-by-allergen-specific-immunotherapy-ameliorate-allergic-airway-disease-in-a-human-mouse-chimeric-model
#5
Caterina Vizzardelli, Miriam Gindl, Simone Roos, Christian Möbs, Birgit Nagl, Felix Zimmann, Veronika Sexl, Lukas Kenner, Alina Neunkirchner, Gerhard J Zlabinger, Winfried F Pickl, Wolfgang Pfützner, Barbara Bohle
BACKGROUND: Allergen-specific immunotherapy (AIT) induces specific blocking antibodies (Ab) which are claimed to prevent IgE-mediated reactions to allergens. Additionally, AIT modulates cellular responses to allergens, e.g. by desensitizing effector cells, inducing regulatory T and B lymphocytes and immune deviation. It is still enigmatic which of these mechanisms mediate(s) clinical tolerance. We sought to address the role of AIT-induced blocking Ab separately from cellular responses in a chimeric human/mouse model of respiratory allergy...
November 21, 2017: Allergy
https://www.readbyqxmd.com/read/29159802/adenovirus-vector-based-prime-boost-vaccination-via-heterologous-routes-induces-cervicovaginal-cd8-t-cell-responses-against-hpv16-oncoproteins
#6
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
#7
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
#8
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
#9
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/29159189/nmdar-encephalitis-passive-transfer-from-man-to-mouse-by-a-recombinant-antibody
#10
Manish Malviya, Sumanta Barman, Kristin S Golombeck, Jesús Planagumà, Francesco Mannara, Nathalie Strutz-Seebohm, Claudia Wrzos, Fatih Demir, Christine Baksmeier, Julia Steckel, Kim Kristin Falk, Catharina C Gross, Stjepana Kovac, Kathrin Bönte, Andreas Johnen, Klaus-Peter Wandinger, Elena Martín-García, Albert J Becker, Christian E Elger, Nikolaj Klöcker, Heinz Wiendl, Sven G Meuth, Hans-Peter Hartung, Guiscard Seebohm, Frank Leypoldt, Rafael Maldonado, Christine Stadelmann, Josep Dalmau, Nico Melzer, Norbert Goebels
Objective: Autoimmune encephalitis is most frequently associated with anti-NMDAR autoantibodies. Their pathogenic relevance has been suggested by passive transfer of patients' cerebrospinal fluid (CSF) in mice in vivo. We aimed to analyze the intrathecal plasma cell repertoire, identify autoantibody-producing clones, and characterize their antibody signatures in recombinant form. Methods: Patients with recent onset typical anti-NMDAR encephalitis were subjected to flow cytometry analysis of the peripheral and intrathecal immune response before, during, and after immunotherapy...
November 2017: Annals of Clinical and Translational Neurology
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
#11
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/29158932/gastric-and-rectal-metastases-from-malignant-melanoma-presenting-with-hypochromic-anemia-and-treated-with-immunotherapy
#12
Pietro Genova, Maria Sorce, Daniela Cabibi, Gaspare Genova, Vittorio Gebbia, Daniela Galanti, Chiara Ancona, Maria Rosaria Valerio
The authors present a case of an 80-year-old Caucasian male with multiple gastric and rectal metastases from malignant melanoma presenting with hypochromic anemia as the sole symptom of disease without evidence of cutaneous and ocular tumor localization. The patient had a medical history positive for malignant lentigo melanoma of the occipital region of the scalp and early stage laryngeal squamous cell carcinoma and prostatic carcinoma treated with radiation therapy. The authors make some considerations on intestinal involvement by metastatic melanoma and discuss the choice of not treating with endoscopic procedures the gastric metastatic lesions most likely responsible for the clinical sign present at diagnosis...
2017: Case Reports in Oncological Medicine
https://www.readbyqxmd.com/read/29158855/clinical-evaluation-of-terap-c-vaccine-in-combined-treatment-with-interferon-and-ribavirin-in-patients-with-hepatitis-c
#13
Dorta Guridi Zaily, Castellanos Fernandez Marlen, Dueñas-Carrera Santiago, Martínez Donato Gillian, Valenzuela Silva Carmen, Cinza Estevez Zurina, Arús Soler Enrique R, Alvarez-Lajonchere Liz, González Fabián Lisset, Lazo Del Vallín Sacha, Ferrer Bataille Elena
Background: An estimated 170 million individuals worldwide are infected with the hepatitis C virus (HCV). Although treatment options using a combination of pegylated interferon and ribavirin (P-IFN/RBV) are available, sustained clearance of the virus is only achieved in approximately 40% of individuals infected with HCV genotype 1. Recent advances in the treatment of HCV using directly acting antiviral agents have been achieved; however, treatment can be very expensive and is associated with substantial side effects...
2017: Current Therapeutic Research, Clinical and Experimental
https://www.readbyqxmd.com/read/29158834/rational-design-of-polymeric-hybrid-micelles-to-overcome-lymphatic-and-intracellular-delivery-barriers-in-cancer-immunotherapy
#14
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
#15
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
#16
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/29158790/synergy-of-purine-scaffold-tlr7-agonist-with-doxorubicin-on-systemic-inhibition-of-lymphoma-in-mouse-model
#17
Dong Gao, Wang Li, Wanmin Wang, Yongguang Cai, Yuhuan Wang, Xiaoling Luo, Chih-Chang Wei
Chemo- and radio-therapy suffer from certain well-recognized drawbacks for lymphoma therapy. Passive immunotherapy with monoclonal antibody has improved outcome for patients with CD20(+) B cell lymphoma, but not for T cell lymphoma. Therefore, novel treatment approaches are clearly required for T cell lymphoma. To date, the combined application targeting TLR7, 8 and 9 has established long-term antitumor immunity. We previously synthesized a purine-scaffold TLR7 agonist named GD5. Here, we report that the intratumoral administration of GD5 combined with doxorubicin (DOX), a conventional chemotherapeutic agent in T cell lymphoma...
2017: Journal of Cancer
https://www.readbyqxmd.com/read/29158788/programmed-death-ligand-1-pd-l1-expression-in-primary-angiosarcoma
#18
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/29158588/immunotherapy-gut-bacteria-modulate-responses-to-pd-1-blockade
#19
David Killock
No abstract text is available yet for this article.
November 21, 2017: Nature Reviews. Clinical Oncology
https://www.readbyqxmd.com/read/29158380/anti-sirp%C3%AE-antibody-immunotherapy-enhances-neutrophil-and-macrophage-antitumor-activity
#20
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
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