STING signaling is a potential immunotherapeutic target in colorectal cancer

Conclusion: We confirmed the distinct STING expression in CRC and demonstrated its independent prognostic value in survival outcomes. STING could be a potential therapeutic target that enhances anti-cancer immune response in CRC.
Source: Journal of Cancer - Category: Cancer & Oncology Authors: Tags: Research Paper Source Type: research

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The stimulator of IFN genes (STING) signaling pathway is a critical link between innate and adaptive immunity and induces antitumor immune responses. STING is expressed in vasculatures, but its role in tumor angiogenesis has not been elucidated. Here, we investigated STING-induced tumor vascular remodeling and the potential of STING-based combination immunotherapy. Endothelial STING expression was correlated with enhanced T cell infiltration and prolonged survival in human colon and breast cancer. Intratumoral STING activation with STING agonists (cGAMP or RR-CDA) normalized tumor vasculatures in implanted and spontaneous ...
Source: Journal of Clinical Investigation - Category: Biomedical Science Authors: Source Type: research
Marjolein Schluck1,2, Roel Hammink1,2, Carl G. Figdor1,2,3, Martijn Verdoes1,3*† and Jorieke Weiden1,2,3*† 1Department of Tumor Immunology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, Netherlands 2Division of Immunotherapy, Oncode Institute, Radboud University Medical Center, Nijmegen, Netherlands 3Institute for Chemical Immunology, Nijmegen, Netherlands Traditional tumor vaccination approaches mostly focus on activating dendritic cells (DCs) by providing them with a source of tumor antigens and/or adjuvants, which in turn activate tumor-reactive T c...
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research
In this study, several biopsies from a patient-derived primary renal-cell carcinoma were analyzed by whole-exome sequencing and aligned to healthy tissue. Next to several shared mutations between different subclones, ca. 23% of the mutations were only found in specific regions of the tumor. Strikingly, a single biopsy of that same tumor only covered around 55% of the total mutational diversity, underlining the need for multi-region sampling. Tracing the order of mutations in different subclones revealed that they develop in a branching fashion from the primary tumor clone, harboring the driver mutation, rather than in a li...
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research
Design of amidobenzimidazole STING receptor agonists with systemic activity, Published online: 07 November 2018; doi:10.1038/s41586-018-0705-yA small-molecule agonist for the cGAS–STING pathway has systemic activity in a mouse model of colon cancer.
Source: Nature AOP - Category: Research Authors: Source Type: research
Nature Nanotechnology 12, 648 (2017). doi:10.1038/nnano.2017.52 Authors: Min Luo, Hua Wang, Zhaohui Wang, Haocheng Cai, Zhigang Lu, Yang Li, Mingjian Du, Gang Huang, Chensu Wang, Xiang Chen, Matthew R. Porembka, Jayanthi Lea, Arthur E. Frankel, Yang-Xin Fu, Zhijian J. Chen &Jinming Gao The generation of tumour-specific T cells is critically important for cancer immunotherapy. A major challenge in achieving a robust T-cell response is the spatiotemporal orchestration of antigen cross-presentation in antigen-presenting cells with innate stimulation. Here, we report a minimalist nanovaccine, comprising a simple physi...
Source: Nature Nanotechnology - Category: Nanotechnology Authors: Tags: Letter Source Type: research
We describe here our finding th at a CD45+ CD11bmid Ly6C+ cell subset transiently accumulated in mouse tumor microenvironment of 4T1 breast cancer, squamous cell carcinomas, CT26 colon cancer, or B16F10 melanoma tissue after intratumoral injection of cGAMP. The accumulated cells displayed a macrophage (M ) phenotype since the cells were positive for F4/80 and MHC class II and negative for Ly6G. Intratumoral cGAMP treatment did not induce M φ accumulation in STING-deficient mice. Depletion of CD8+ T cell using anti-CD8 mAb impaired the anti-tumor effects of cGAMP treatment. Depletion of the M φ using clodronate lipo...
Source: Cancer Immunology, Immunotherapy - Category: Cancer & Oncology Source Type: research
Conclusions: In contrast to DNA-sensing events in viral infections or autoimmunity,cGAS-STING-IFNB signaling is disrupted in colorectal cancer. The expression levels ofcGAS,RNASEH2B,RNASEH2C, andSAMHD1 could be prognostic markers of colorectal cancer.Oncology 2017;92:115-124
Source: Oncology - Category: Cancer & Oncology Source Type: research
CONCLUSIONS: In contrast to DNA-sensing events in viral infections or autoimmunity, cGAS-STING-IFNB signaling is disrupted in colorectal cancer. The expression levels of cGAS, RNASEH2B, RNASEH2C, and SAMHD1 could be prognostic markers of colorectal cancer. PMID: 27988520 [PubMed - as supplied by publisher]
Source: Oncology - Category: Cancer & Oncology Authors: Tags: Oncology Source Type: research
Abstract Novel immunotherapy approaches are transforming the treatment of cancer, yet many patients remain refractory to these agents. One hypothesis is that immunotherapy fails because of a tumor microenvironment that fails to support recruitment of immune cells including CD8+ T cells. Therefore, new approaches designed to initiate a de novo anti-tumor immune response from within the tumor microenvironment are being pursued. Recent evidence has indicated that spontaneous activation of the Stimulator of Interferon Genes (STING) pathway within tumor-resident dendritic cells leads to type I interferon (IFN) producti...
Source: Clinical Cancer Research - Category: Cancer & Oncology Authors: Tags: Clin Cancer Res Source Type: research
Spontaneous tumor-initiated T cell priming is dependent on IFN-β production by tumor-resident dendritic cells. Based on recent observations indicating that IFN-β expression was dependent upon activation of the host STING (Stimulator of Interferon Genes) pathway, we hypothesized that direct engagement of STING through intratumoral administration of specific agonists would result in effective anti-tumor therapy. To this end, we generated novel synthetic cyclic dinucleotide (CDN) derivatives with superior STING-activating and anti-tumor properties. The most potent molecule contains a 2′-5′ and 3′-5...
Source: Cancer Research - Category: Cancer & Oncology Authors: Tags: Clinical Research (Excluding Clinical Trials) Source Type: research
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