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Cancer AND Immune System

Daniel S Chen, Herbert Hurwitz
Cancer immunotherapy (CIT) has transformed cancer treatment. In particular, immunotherapies targeting the programmed death ligand 1 (PD-L1)/programmed death 1 pathway have demonstrated durable clinical benefit in some patients. However, CIT combinations may create a more favorable environment in which to maximize the potential of the immune system to eliminate cancer. Here we describe 3 key mechanisms related to vascular endothelial growth factor (VEGF)-mediated immunosuppression: inhibition of dendritic cell maturation, reduction of T-cell tumor infiltration, and promotion of inhibitory cells in the tumor microenvironment; supporting data are also described...
July 2018: Cancer Journal
Xing Liu, Yiming Li, Zhiyan Sun, Shaowu Li, Kai Wang, Xing Fan, Yuqing Liu, Lei Wang, Yinyan Wang, Tao Jiang
The presence of contrast enhancement (CE) on magnetic resonance (MR) imaging is conventionally regarded as an indicator for tumor malignancy. However, the biological behaviors and molecular mechanism of enhanced tumor are not well illustrated. The aim of this study was to investigate the molecular profiles associated with anaplastic gliomas (AGs) presenting CE on postcontrast T1-weighted MR imaging. In this retrospective database study, RNA sequencing and MR imaging data of 91 AGs from the Cancer Genome Atlas (TCGA) and 64 from the Chinese Glioma Genome Atlas (CGGA) were collected...
August 16, 2018: Cancer Medicine
Yanming Sun, Zhitao Yao, Zhihua Zhao, Haifeng Xiao, Mengting Xia, Xiaojun Zhu, Xuelu Jiang, Chuntao Sun
Ovarian cancer has the highest mortality rate and is the most common of all gynecologic malignancies. Novel treatments for ovarian cancer are urgently required to improve outcomes and the overall survival of patients. The present study investigated whether immunotherapy with natural killer (NK) cells affected the survival of mice with ovarian cancer. Results analysis identified adjunctive NK cells as a potential therapeutic method in ovarian cancer. Patient-derived ovarian cells were isolated, cultured and subsequently injected subcutaneously into immune deficient BALB/c-nude mice...
August 2018: Experimental and Therapeutic Medicine
Jun Lu, Long-Long Cao, Ping Li, Jian-Wei Xie, Jia-Bin Wang, Jian-Xian Lin, Qi-Yue Chen, Mi Lin, Ru-Hong Tu, Chang-Ming Huang, Chao-Hui Zheng
Background: Determining preferences regarding the benefits of adjuvant chemotherapy (AC) for stage I GC is critical. Methods: We retrospectively reviewed 1069 patients with pathologically confirmed stage I GC who underwent R0 gastrectomy between 2006 and 2014. Univariate and multivariate survival analyses were conducted. Systemic inflammation factors were used to develop a scoring system for predicting AC benefits. Results: With a median follow-up of 47 months (range 3-113 months), the 5-year overall survival (OS) rate was 90...
2018: Gastroenterology Research and Practice
Sarah Schulze, Christian Stöß, Miao Lu, Baocai Wang, Melanie Laschinger, Katja Steiger, Felicitas Altmayr, Helmut Friess, Daniel Hartmann, Bernhard Holzmann, Norbert Hüser
Stimulation of cytosolic nucleic acid sensors of innate immunity by pathogen-derived nucleic acids is important for antimicrobial defence, but stimulation through self-derived nucleic acids may contribute to autoinflammation and cancer. DNA sensing in the cytosol requires the stimulator of interferon genes (STING), while cytosolic RNA sensors use mitochondrial antiviral-signalling protein (MAVS). In a murine model of two-thirds hepatectomy, combined deficiency of MAVS and STING resulted in strongly impaired hepatocyte proliferation and delayed recovery of liver mass...
August 16, 2018: Scientific Reports
Andrea Zhe Ern Lee, Louise Soo Yee Tan, Chwee Ming Lim
Undifferentiated Nasopharyngeal carcinoma (NPC) is ubiquitously identified with the Epstein-Barr virus (EBV), making this cancer a suitable candidate for cellular-based immunotherapy (CBI) due to its expression of potentially targetable tumor-associated viral antigens. Various preclinical and clinical studies have explored the use of cytotoxic T cells (CTLs), tumor-infiltrating lymphocytes (TILs), natural killer (NK) cells, and dendritic cells (DCs) in the treatment of both refractory and locally advanced NPC with some success...
September 2018: Oral Oncology
Yang Liu, Yinping Dong, Li Kong, Fang Shi, Hui Zhu, Jinming Yu
Radiotherapy (RT) is used routinely as a standard treatment for more than 50% of patients with malignant tumors. The abscopal effect induced by local RT, which is considered as a systemic anti-tumor immune response, reflects the regression of non-irradiated metastatic lesions at a distance from the primary site of irradiation. Since the application of immunotherapy, especially with immune checkpoint inhibitors, can enhance the systemic anti-tumor response of RT, the combination of RT and immunotherapy has drawn extensive attention by oncologists and cancer researchers...
August 16, 2018: Journal of Hematology & Oncology
Amir A Sadighi Akha
The world is witnessing a rapid demographic shift towards an older population, a trend with major medical, social, economic and political implications. Aging is a multifaceted process, involving numerous molecular and cellular mechanisms in the context of different organ systems. A crucial component of aging is a set of functional and structural alterations in the immune system that can manifest as a decreased ability to fight infection, diminished response to vaccination, increased incidence of cancer, higher prevalence of autoimmunity and constitutive low-grade inflammation, among others...
August 13, 2018: Journal of Immunological Methods
Muhammad Khan, Jie Lin, Guixiang Liao, Yunhong Tian, Yingying Liang, Rong Li, Mengzhong Liu, Yawei Yuan
BACKGROUND: Recently, immune checkpoint inhibitors have shown survival advantage over chemotherapy in the treatment of advanced non-small cell lung cancer (NSCLC). This meta-analysis was conducted to gather and analyze the available evidence (Evidence level I; Randomized Controlled Trials) comparing efficacy and safety of anti-programmed cell death-1 (PD1)/programmed cell death ligand 1 (PD-L1) therapies and chemotherapy in the treatment of advanced NSCLC. METHODS: A search strategy was devised to identify the randomized controlled trials (RCTs) using electronic databases of PubMed, Cochrane Library, and Web of Science...
August 2018: Medicine (Baltimore)
Stefanie Pektor, Lina Hilscher, Kerstin C Walzer, Isabelle Miederer, Nicole Bausbacher, Carmen Loquai, Mathias Schreckenberger, Ugur Sahin, Mustafa Diken, Matthias Miederer
BACKGROUND: [18 F]Fluoro-2-deoxy-2-D-glucose positron emission tomography (FDG-PET) is commonly used in the clinic for diagnosis of cancer and for follow-up of therapy outcome. Additional to the well-established value in tumor imaging, it bears potential to depict immune processes in modern immunotherapies. T cells enhance their glucose consumption upon activation and are crucial effectors for the success of such novel therapies. In this study, we analyzed the T cell immunity in spleen after antigen-specific stimulation of T cells via highly innovative RNA-based vaccines using FDG-PET/MRI...
August 15, 2018: EJNMMI Research
Thomas Richards, Elena Brin
Indoleamine 2,3-dioxygenase 1 (IDO1) is a new immune-oncology target and its inhibitors have shown promise in the clinic especially in combination with other immune-stimulating agents. Here we describe two robust cell-based assays for screening IDO1 inhibitors. Both assays can be easily adopted by most laboratories and utilized for screening of IDO1 inhibitors. Endogenous IDO1 expression is induced in a cancer cell line with interferon gamma and its activity is assessed by measuring kynurenine secreted into the media...
July 20, 2018: Oncotarget
Jenny Rubin, Sharmineh Mansoori, Kristin Blom, Malin Berglund, Lena Lenhammar, Claes Andersson, Angelica Loskog, Mårten Fryknäs, Peter Nygren, Rolf Larsson
Mebendazole (MBZ) was recently shown to induce a tumor suppressive M1 phenotype in THP-1 monocytes and macrophages. In the present study the immune effects of MBZ was further investigated using human peripheral blood mononuclear cells (PBMCs) co-cultured with tumour cells. The Biomap platform was used to screen for biomarkers induced from MBZ exposed co-cultures of T-cell receptor activated PBMCs, HT29 colon cancer cells and either human fibroblasts or human umbilical vein endothelial cells (HUVEC) cells. In these co-culture systems MBZ at 0...
July 20, 2018: Oncotarget
Jing Shi, Tian-Tian Ma, Hua-Sheng Liu
In recent years, with the incidence of malignant tumors increasing year by year, its treatment has been made great progress on the basis of traditional treatments such as surgery, radiotherapy and chemotherapy, it mainly focuses on rapid development of cellular immunotherapy. The efficacy of dendritic cells combined with cytokine induced killer cell (DC-CIK) immunotherapy for cancer patients is positive, it shows good antitumor activities and the abilities to reconstruct and enhance the immune system of tumor patients in clinical application, it has potential application value...
August 2018: Zhongguo Shi Yan Xue Ye Xue za Zhi
Jonas Steenbrugge, Koen Breyne, Kristel Demeyere, Olivier De Wever, Niek N Sanders, Wim Van Den Broeck, Cecile Colpaert, Peter Vermeulen, Steven Van Laere, Evelyne Meyer
BACKGROUND: Murine breast cancer models relying on intraductal tumor cell inoculations are attractive because they allow the study of breast cancer from early ductal carcinoma in situ to metastasis. Using a fully immunocompetent 4T1-based intraductal model for triple-negative breast cancer (TNBC) we aimed to investigate the immunological responses that guide such intraductal tumor progression, focusing on the prominent role of macrophages. METHODS: Intraductal inoculations were performed in lactating female mice with luciferase-expressing 4T1 mammary tumor cells either with or without additional RAW264...
August 15, 2018: Journal of Experimental & Clinical Cancer Research: CR
Yingbin Shen, Tianyao Hao, Shiyi Ou, Churan Hu, Long Chen
Vaccines show great potential for both prophylactic and therapeutic use in infections, cancer, and other diseases. With the rapid development of bio-technologies and materials sciences, nanomaterials are playing essential roles in novel vaccine formulations and can boost antigen effectiveness by operating as delivery systems to enhance antigen processing and/or as immune-potentiating adjuvants to induce or potentiate immune responses. The effect of nanoparticles in vaccinology showed enhanced antigen stability and immunogenicity as well as targeted delivery and slow release...
February 1, 2018: MedChemComm
Magali Trayssac, Yusuf A Hannun, Lina M Obeid
Aging is defined as the progressive deterioration of physiological function with age. Incidence of many pathologies increases with age, including neurological and cardiovascular diseases and cancer. Aging tissues become less adaptable and renewable, and cells undergo senescence, a process by which they "irreversibly" stop dividing. Senescence has been shown to serve as a tumor suppression mechanism with clear desirable effects. However, senescence also has deleterious consequences, especially for cardiovascular, metabolic, and immune systems...
July 2, 2018: Journal of Clinical Investigation
Jinming Yang, Amrendra Kumar, Anna E Vilgelm, Sheau-Chiann Chen, Gregory D Ayers, Sergey V Novitskiy, Sebastian Joyce, Ann Richmond
The chemokine receptor, CXCR4, is involved in cancer growth, invasion, and metastasis. Several promising CXCR4 antagonists have been shown to halt tumor metastasis in preclinical studies, and clinical trials evaluating the effectiveness of these agents in cancer patients are ongoing. However, the impact of targeting CXCR4 specifically on immune cells is not clear. Here we demonstrate that genetic deletion of CXCR4 in myeloid cells (CXCR4MyeΔ/Δ) enhances the antitumor immune response, resulting in significantly reduced melanoma tumor growth...
August 14, 2018: Cancer Immunology Research
Angus G Dalgleish, Satvinder Mudan, Alberto Fusi
BACKGROUND: The use of checkpoint inhibitors (ipilimumab, pembrolizumab, nivolumab) has revolutionised the treatment of metastatic melanoma. However still more than the half the patients do not respond to single-agent immunotherapy. This has led to the development of combining these agents in an attempt to enhance the anti-cancer activity. More than 300 different studies with 15 different drug doses are currently ongoing. Combining different checkpoint inhibitors (CPIs) does indeed lead to an increase in response rate, but this is associated with significant toxicity...
August 14, 2018: Journal of Translational Medicine
Adi Sharbi-Yunger, Mareike Grees, Cafri Gal, David Bassan, Stefan B Eichmüller, Esther Tzehoval, Jochen Utikal, Viktor Umansky, Lea Eisenbach
For many years, clinicians and scientists attempt to develop methods to stimulate the immune system to target malignant cells. Recent data suggest that effective cancer vaccination requires combination immunotherapies to overcome tumor immune evasion. Through presentation of both MHC-I and II molecules, DCs based vaccine platforms are effective in generating detectable CD4 and CD8 T cell responses against tumor associated antigens. Several platforms include DC transfection with mRNA of the desired tumor antigen...
August 14, 2018: International Journal of Cancer. Journal International du Cancer
Valentina Pucino, Danilo Cucchi, Claudio Mauro
Inflammation is associated with the accumulation of lactate at sites of tumour growth and inflammation. Lactate initiates tissue responses contributing to disease. We discuss the potential of targeting lactate transporters in the treatment of cancer and inflammatory conditions. Areas covered: Lactate is the product of glycolysis, which is considered to be a waste metabolite and a fuel for oxidative cells. It is also an active signalling molecule with immunomodulatory and angiogenic properties. They are the consequence of lactate binding to membrane receptor(s) or being transported through specific carrier-mediated transporters across the cellular membrane...
August 14, 2018: Expert Opinion on Therapeutic Targets
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