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Immune check point

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https://www.readbyqxmd.com/read/27898465/the-intragraft-microenvironment-as-a-central-determinant-of-chronic-rejection-or-local-immunoregulation-tolerance
#1
Johannes Wedel, Hironao Nakayama, Nora M Kochupurakkal, Josephine Koch, Michael Klagsbrun, Diane R Bielenberg, David M Briscoe
PURPOSE OF REVIEW: Chronic rejection is associated with persistent mononuclear cell recruitment, endothelial activation and proliferation, local tissue hypoxia and related biology that enhance effector immune responses. In contrast, the tumor microenvironment elicits signals/factors that inhibit effector T cell responses and rather promote immunoregulation locally within the tissue itself. The identification of immunoregulatory check points and/or secreted factors that are deficient within allografts is of great importance in the understanding and prevention of chronic rejection...
November 24, 2016: Current Opinion in Organ Transplantation
https://www.readbyqxmd.com/read/27894751/polymerase-%C3%AE%C2%B5-pole-ultra-mutation-in-uterine-tumors-correlates-with-t-lymphocyte-infiltration-and-increased-resistance-to-platinum-based-chemotherapy-in-vitro
#2
Stefania Bellone, Eliana Bignotti, Silvia Lonardi, Francesca Ferrari, Floriana Centritto, Alice Masserdotti, Francesca Pettinella, Jonathan Black, Gulden Menderes, Gary Altwerger, Pei Hui, Salvatore Lopez, Christopher de Haydu, Elena Bonazzoli, Federica Predolini, Luca Zammataro, Emiliano Cocco, Federico Ferrari, Antonella Ravaggi, Chiara Romani, Fabio Facchetti, Enrico Sartori, Franco E Odicino, Dan-Arin Silasi, Babak Litkouhi, Elena Ratner, Masoud Azodi, Peter E Schwartz, Alessandro D Santin
OBJECTIVE: Up to 12% of all endometrial-carcinomas (EC) harbor DNA-polymerase-ε-(POLE) mutations. It is currently unknown whether the favorable prognosis of POLE-mutated EC is derived from their low metastatic capability, extraordinary number of somatic mutations thus imparting immunogenicity, or a high sensitivity to chemotherapy. METHODS: Polymerase-chain-reaction-amplification and Sanger-sequencing were used to test for POLE exonuclease-domain-mutations (exons 9-14) 131 EC...
November 25, 2016: Gynecologic Oncology
https://www.readbyqxmd.com/read/27893699/nivolumab-induced-severe-akathisia-in-an-advanced-lung-cancer-patient
#3
Jiro Abe, Taku Sato, Ryota Tanaka, Toshimasa Okazaki, Satomi Takahashi
BACKGROUND Nivolumab is an anti-PD-1 immune checkpoint inhibitor that was recently developed for cancer immunotherapy. In the clinical trials of nivolumab, its adverse effects were reported to be less likely than those of conventional anti-cancer agents; however, after practical clinical distribution, it has come to be known that nivolumab induces various immune-related adverse events. CASE REPORT A 58-year-old male with a recurrence of lung adenocarcinoma was treated with nivolumab. Only four days after the initial administration of nivolumab, the patient presented with unbearable restlessness and distress that was resistant to all therapeutic agents used, and it gradually became worse...
November 23, 2016: American Journal of Case Reports
https://www.readbyqxmd.com/read/27860539/epitope-specific-antitumor-immunity-suppresses-tumor-spread-in-papillary-thyroid-cancer
#4
Margret Ehlers, Anne Kuebart, Hubertus Hautzel, Juergen Enczmann, Anna-Carinna Reis, Matthias Haase, Stephanie Allelein, Till Dringenberg, Christine Schmid, Matthias Schott
CONTEXT: Papillary thyroid cancer (PTC) is characterized by a lymphocytic infiltration. PTC patients with lymphocytic infiltration may have a better clinical outcome. OBJECTIVE: Characterization of tumor epitope-specific immunity and correlation analyses with the clinical outcome. PATIENTS: 150 PTC patients; 40 Hashimoto's thyroiditis (HT) patients; 21 healthy controls; 27.239 healthy Caucasians (for HLA typing). MAIN OUTCOME MEASURES: HLA class I restricted thyroperoxidase (TPO) and thyroglobulin (Tg) epitope-specific T cells (tetramer analyses), correlation analyses between HLA class II phenotypes, T cell immunity, and the clinical course...
November 18, 2016: Journal of Clinical Endocrinology and Metabolism
https://www.readbyqxmd.com/read/27771969/vinflunine-for-the-treatment-of-non-small-cell-lung-cancer
#5
C Genova, A Alama, S Coco, E Rijavec, M G Dal Bello, I Vanni, F Biello, G Barletta, G Rossi, F Grossi
Vinflunine belongs to the class of vinca alkaloids and acts by disrupting the microtubule dynamics during cell cycle; this agent is currently available for previously treated advanced transitional cell carcinoma in Europe. The aim of this invited review is to evaluate the potential role of vinflunine for the treatment of non-small cell lung cancer (NSCLC). Areas covered: The potential role of vinflunine in NSCLC is discussed on the basis of the available data, including full papers and meeting abstracts. Relevant preclinical studies describing the pharmacological properties of vinflunine are also included...
November 1, 2016: Expert Opinion on Investigational Drugs
https://www.readbyqxmd.com/read/27754760/combining-mpdl3280a-with-adoptive-cell-immunotherapy-exerts-better-antitumor-effects-against-cervical-cancer
#6
Yi Zheng, Yicheng Yang, Shu Wu, Yongqiang Zhu, Xiaolong Tang, Xiaopeng Liu
As the second most common gynecologic malignant tumors with a high mortality rate, cervical cancer jeopardizes women's life worldwide. The low cure rate in cervical cancer patients is mainly attributed to the lack of effective therapies. One feasible novel strategy is to develop immune-based approaches such as adoptive cell immunotherapy of DCCIKs which represents a promising nontoxic antineoplastic immunotherapy preferred in clinic practice. However, the therapeutic effect is not as efficient as anticipated...
October 18, 2016: Bioengineered
https://www.readbyqxmd.com/read/27750243/recent-trends-in-the-management-of-hepatocellular-carcinoma-with-special-emphasis-on-treatment-with-regorafenib-and-immune-checkpoint-inhibitors
#7
Masatoshi Kudo
Hepatocellular carcinoma (HCC) is the fifth most common cancer and the third leading cause of cancer deaths worldwide. Sonazoid-enhanced ultrasound and gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid-enhanced MRI are the most important imaging modalities in diagnosing HCC. There are 2 non-contradictory HCC treatment algorithms in Japan. Hepatic arterial infusion chemotherapy plays an important role in the treatment of advanced HCC with main or branch portal vein invasion. Regorafenib, as a second-line systemic treatment, prolongs survival in patients with intermediate and advanced HCC who progressed on sorafenib...
2016: Digestive Diseases
https://www.readbyqxmd.com/read/27704269/linked-cd4-t-cell-help-broadening-immune-attack-against-cancer-by-vaccination
#8
Natalia Savelyeva, Alex Allen, Warayut Chotprakaikiat, Elena Harden, Jantipa Jobsri, Rosemary Godeseth, Yidao Wang, Freda Stevenson, Christian Ottensmeier
In the last decade, immunotherapy with monoclonal antibodies targeting immunological check points has become a breakthrough therapeutic modality for solid cancers. However, only up to 50 % of patients benefit from this powerful approach. For others vaccination might provide a plausible addition or alternative. For induction of effective anticancer immunity CD4+ T cell help is required, which is often difficult to induce to self cancer targets because of tolerogenic mechanisms. Our approach for cancer vaccines has been to incorporate into the vaccine design sequences able to activate foreign T cell help, through genetically linking cancer targets to microbial sequences (King et al...
October 5, 2016: Current Topics in Microbiology and Immunology
https://www.readbyqxmd.com/read/27647396/-current-status-and-future-prospect-of-internal-medicine-treatment-for-advanced-esophageal-cancer
#9
F Wang, Q X Fan
Esophageal cancer (EC) is one of common malignant tumors, and the incidence and mortality of EC in China rank the first place in the world. Because of the occult onset, the early atypical symptoms, and the lack of effective early diagnostic methods, most of patients are diagnosed at an advanced stage of the disease and lost the chance of surgery. Comprehensive treatment including palliative medical treatment, molecular targeted therapy, immunotherapy and so on is appropriate for these patients. How to choose the chemotherapy regimen and formulate reasonable treatment plan has become a hot spot in clinical research...
September 23, 2016: Zhonghua Zhong Liu za Zhi [Chinese Journal of Oncology]
https://www.readbyqxmd.com/read/27609016/gastric-cancer-somatic-genetics-as-a-guide-to-therapy
#10
Xiao-Ying Zhang, Pei-Ying Zhang
Gastric cancer is the leading cause of cancer-related mortality across the world, with poor prognosis and a median overall survival of ≤12 months for advanced stage gastric cancer. Environmental, genetic and other predisposing factors contribute to the development of gastric cancer and a predominant factor was found to be infection of Helicobacter pylori Advances in understanding the deranged signalling pathways that are critical for normal cellular homeostasis helped in the development of novel drugs that target specific proteins and pathways to curtail the growth of gastric cancer...
September 8, 2016: Journal of Medical Genetics
https://www.readbyqxmd.com/read/27587244/-comparison-of-immune-reconstitution-at-early-stage-after-unmanipulated-haploidentical-stem-cell-transplantation-between-high-and-standard-risk-philadelphia-chromosome-negative-acute-lymphoblastic-leukemia-patients-in-cr1
#11
Z L Bian, Y J Chang, L P Xu, Y Wang, X H Zhang, K Y Liu, X J Huang
OBJECTIVE: To compare the early stage immune reconstitution of high- and standard-risk Philadelphia chromosome- negative acute lymphoblastic leukemia (ALL) CR1 patients who had haploidentical blood and marrow stem cell transplantation (HBMT). METHODS: A total of 49 Ph-negative ALL CR1 patients who received HBMT and had complete early stage immune reconstitution data(+30, +60 and +90 d post transplantation) from Jan. 2010 to Dec. 2012 were enrolled. Immunophenotyping for B and T lymphocytes was performed post HBMT via flow cytometry...
August 14, 2016: Zhonghua Xue Ye Xue za Zhi, Zhonghua Xueyexue Zazhi
https://www.readbyqxmd.com/read/27563660/future-perspectives-in-cancer-immunotherapy
#12
Marinos Tsiatas, Giannis Mountzios, Giuseppe Curigliano
The advent of immunotherapy has transformed the treatment paradigm of several solid tumors and is expected to influence the therapeutic algorithm even more in the future following the results of numerous ongoing clinical trials in a wide range of malignancies. Exploiting the anti-cancer effect of the immune system with the use of vaccines, viral vectors, and more lately with immune check-point inhibitors and chimeric antigen receptor modification, has been proven a successful therapeutic strategy in a broad spectrum of tumors...
July 2016: Annals of Translational Medicine
https://www.readbyqxmd.com/read/27528363/new-approaches-in-glioblastoma-multiforme-the-potential-role-of-immune-check-point-inhibitors
#13
Francesca De Felice, Daniela Musio, Raffaele Cassese, Giovanni Luca Gravina, Vincenzo Tombolini
BACKGROUND: Glioblastoma multiforme (GBM) is the most frequent brain tumor. Despite recent advances in treatment approaches the prognosis remains poor, with a median overall survival of 14.6 months. Immunotherapy is the subject of ongoing research and its benefit is becoming evident in other malignancies. Immune check-points such as cytotoxic T lymphocyte associated antigen 4 (CTLA-4), programmed cell death receptor (PD-1) and indoleamine 2,3-dioxygenase (IDO) reduce immune response. OBJECTIVE: To clarify the role of immune check point inhibitors in GBM management...
August 13, 2016: Current Cancer Drug Targets
https://www.readbyqxmd.com/read/27500894/role-of-clinical-pharmacology-in-the-development-and-approval-of-immunotherapies-targeting-immune-checkpoints
#14
A Rahman
Immune surveillance plays a critical role in preventing the development and progression of cancer. Immune modulators, such as interferon-gamma or interleukin-2, have been a part of the cancer treatment armament over the past few decades. However, new understandings regarding the role of the costimulatory and coinhibitory molecules associated with T-cells and antigen-presenting cells as well as tumor necrosis factor receptors and ligands have ushered the new era of immunotherapy for cancer treatment. We now know that primary cancer cells evade screening by the innate immune system, proliferate, and form metastases by upregulating immune inhibitory pathways referred to as immune checkpoints...
August 7, 2016: Clinical Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/27486176/regression-of-chemotherapy-resistant-polymerase-%C3%AE%C2%B5-pole-ultra-mutated-and-msh6-hyper-mutated-endometrial-tumors-with-nivolumab
#15
Alessandro D Santin, Stefania Bellone, Natalia Buza, Jungmin Choi, Peter E Schwartz, Joseph Schlessinger, Richard P Lifton
PURPOSE: The management of endometrial carcinoma no longer amenable to treatment with surgery or radiotherapy has not improved significantly with modern chemotherapy. Alternative therapeutic options are desperately needed. EXPERIMENTAL DESIGN: We describe 2 heavily pretreated patients with recurrent disease refractory to surgery, radiotherapy, and chemotherapy who were treated with the anti-PD-1 immune checkpoint inhibitor nivolumab. RESULTS: Patient #1 harbored an ultra-mutated tumor (mutation load/MB = 117...
December 1, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/27470448/delivery-of-therapeutics-with-nanoparticles-what-s-new-in-cancer-immunotherapy
#16
Flavia Fontana, Dongfei Liu, Jouni Hirvonen, Hélder A Santos
The application of nanotechnology to the treatment of cancer or other diseases has been boosted during the last decades due to the possibility to precise deliver drugs where needed, enabling a decrease in the drug's side effects. Nanocarriers are particularly valuable for potentiating the simultaneous co-delivery of multiple drugs in the same particle for the treatment of heavily burdening diseases like cancer. Immunotherapy represents a new concept in the treatment of cancer and has shown outstanding results in patients treated with check-point inhibitors...
July 29, 2016: Wiley Interdisciplinary Reviews. Nanomedicine and Nanobiotechnology
https://www.readbyqxmd.com/read/27393516/intracranial-response-to-nivolumab-in-nsclc-patients-with-untreated-or-progressing-cns-metastases
#17
Elizabeth Dudnik, Shlomit Yust-Katz, Hovav Nechushtan, Daniel A Goldstein, Alona Zer, Dov Flex, Tali Siegal, Nir Peled
Central nervous system (CNS) metastases occur in 30% of patients with advanced non-small cell lung cancer (NSCLC). Localized treatments targeting CNS metastases result in delays in systemic therapy administration and are associated with neurocognitive impairment. Nivolumab is an immune check-point inhibitor that is approved as a second-line treatment of NSCLC. Data regarding the intracranial activity of nivolumab is lacking. We retrospectively reviewed the efficacy and safety of nivolumab in five patients with advanced NSCLC and new/progressing intracranial metastases...
August 2016: Lung Cancer: Journal of the International Association for the Study of Lung Cancer
https://www.readbyqxmd.com/read/27334853/follicular-lymphoma-the-role-of-the-tumor-microenvironment-in-prognosis
#18
Takumi Sugimoto, Takashi Watanabe
The microenvironment of follicular lymphoma (FL) is composed of tumor-infiltrating CD8(+) T cells, follicular regulatory T cells, lymphoma-associated macrophages and mast cells, follicular helper T cells, follicular dendritic cells, and follicular reticular cells, all of which have been reported to have relevance in the prognosis of FL patients. In addition, some of these cells play a role in the histologic transformation of FL. Macrophages contribute to a poor prognosis in FL patients treated in the pre-rituximab era, but are associated with good prognosis in those treated in the rituximab era...
2016: Journal of Clinical and Experimental Hematopathology: JCEH
https://www.readbyqxmd.com/read/27266327/triggering-receptor-expressed-on-myeloid-cells-and-5-adenosine-monophosphate-activated-protein-kinase-in-the-inflammatory-response-a-potential-therapeutic-target
#19
Finosh G Thankam, Matthew F Dilisio, Kaitlin A Dougherty, Nicholas E Dietz, Devendra K Agrawal
INTRODUCTION: The events in the cellular and molecular signaling triggered during inflammation mitigate tissue healing. The metabolic check-point control mediated by 5'-adenosine monophosphate-activated protein kinase (AMPK) is crucial for switching the cells into an activated state capable of mediating inflammatory events. The cell metabolism involved in the inflammatory response represents a potential therapeutic target for the pharmacologic management of inflammation. AREAS COVERED: In this article, a critical review is presented on triggering receptor expressed on myeloid cell (TREM) receptors and their role in the inflammatory responses, as well as homeostasis between different TREM molecules and their regulation...
June 8, 2016: Expert Review of Clinical Immunology
https://www.readbyqxmd.com/read/27191652/expression-of-pd-1-on-cd4-t-cells-in-peripheral-blood-associates-with-poor-clinical-outcome-in-non-small-cell-lung-cancer
#20
Hong Zheng, Xin Liu, Jianhong Zhang, Shawn J Rice, Matthias Wagman, Yaxian Kong, Liuluan Zhu, Junjia Zhu, Monika Joshi, Chandra P Belani
Recent success of using agents inhibiting the major immune check point, programmed cell death-1 (PD-1) pathway, offers a great promise for effective cancer therapy. Two blocking antibodies for PD-1, nivolumab and pembrolizumab have recently been approved for treating advanced recurrent non-small cell lung cancer (NSCLC). Activation of PD-1 on T cells and PD-L1 on tumor cells or antigen presenting cells leads to T cell exhaustion and ultimately tumor growth. In this study, we performed flow cytometry analysis of peripheral blood samples collected from patients with advanced NSCLC at initial diagnosis...
May 12, 2016: Oncotarget
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