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Immune Colon Cancer

Shu Wen Wen, Jaclyn Sceneay, Luize G Lima, Christina Sf Wong, Melanie Becker, Sophie Krumeich, Richard J Lobb, Vanessa Castillo, Ke Ni Wong, Sarah Ellis, Belinda S Parker, Andreas Moller
Small membranous secretions from tumor cells, termed exosomes, contribute significantly to intercellular communication and subsequent reprogramming of the tumor microenvironment. Here we use optical imaging to determine that exogenously administered fluorescently-labeled exosomes derived from highly metastatic murine breast cancer cells, distributed predominantly to the lung of syngeneic mice, a frequent site of breast cancer metastasis. At the sites of accumulation, exosomes were taken up by CD45+ bone marrow-derived cells...
October 19, 2016: Cancer Research
Xingwei Jiang, Tingting Zhou, Yan Xiao, Jiahui Yu, Shuaijie Dou, Guojiang Chen, Renxi Wang, He Xiao, Chunmei Hou, Wei Wang, Qingzhu Shi, Jiannan Feng, Yuanfang Ma, Beifen Shen, Yan Li, Gencheng Han
T cell Ig mucin-3 (Tim-3), an immune checkpoint inhibitor, shows therapeutic potential. However, the molecular mechanism by which Tim-3 regulates immune responses remains to be determined. In particular, very little is known about how Tim-3 works in innate immune cells. Here, we demonstrated that Tim-3 is involved in the development of tumor-promoting M2 macrophages in colon cancer. Manipulation of the Tim-3 pathway significantly affected the polarization status of intestinal macrophages and the progression of colon cancer...
2016: Oncoimmunology
Xiao-Wen Zhu, Hai-Zhen Zhu, You-Qing Zhu, Mao-Hui Feng, Jian Qi, Zhi-Fen Chen
The mechanism underlying CD4(+)CD25(+)Foxp3(+) regulatory T cells (Tregs) promoting the development of colorectal cancer (CRC) was elucidated in the present study. Forty-eight cases of colorectal carcinomas, 22 cases of colon polyps and 21 cases of normal colorectal tissues were collected. The correlation among Foxp3, IL-10 and Stat3, and the clinical relevance of these three indexes were analyzed. The results showed that the levels of Foxp3 expressed in infiltrating CD4(+)CD25(+)Foxp3(+)Tregs, and IL-10 and Stat3 in CRC tissues were all significantly higher than those in polypus tissues and normal colon tissues (P< 0...
October 2016: Journal of Huazhong University of Science and Technology. Medical Sciences
Ruoxu Dou, Reiko Nishihara, Yin Cao, Tsuyoshi Hamada, Kosuke Mima, Atsuhiro Masuda, Yohei Masugi, Yan Shi, Mancang Gu, Wanwan Li, Annacarolina da Silva, Katsuhiko Nosho, Xuehong Zhang, Jeffrey A Meyerhardt, Edward L Giovannucci, Andrew T Chan, Charles S Fuchs, Zhi Rong Qian, Shuji Ogino
Experimental evidence suggests that the let-7 family of noncoding RNAs suppresses adaptive immune responses, contributing to immune evasion by the tumor. We hypothesized that the amount of let-7a and let-7b expression in colorectal carcinoma might be associated with limited T-lymphocyte infiltrates in the tumor microenvironment and worse clinical outcome. Utilizing the molecular pathological epidemiology resources of 795 rectal and colon cancers in two U.S.-nationwide prospective cohort studies, we measured tumor-associated let-7a and let-7b expression levels by quantitative reverse-transcription PCR, and CD3(+), CD8(+), CD45RO (PTPRC)(+), and FOXP3(+) cell densities by tumor tissue microarray immunohistochemistry and computer-assisted image analysis...
October 13, 2016: Cancer Immunology Research
Darlene A Monlish, Sima T Bhatt, Laura G Schuettpelz
Toll-like receptors (TLRs) are a family of pattern recognition receptors that shape the innate immune system by identifying pathogen-associated molecular patterns and host-derived damage-associated molecular patterns. TLRs are widely expressed on both immune cells and non-immune cells, including hematopoietic stem and progenitor cells, effector immune cell populations, and endothelial cells. In addition to their well-known role in the innate immune response to acute infection or injury, accumulating evidence supports a role for TLRs in the development of hematopoietic and other malignancies...
2016: Frontiers in Immunology
Caroline H Johnson, Mary E Spilker, Laura Goetz, Scott N Peterson, Gary Siuzdak
The role of the host microbiome has come to the forefront as a potential modulator of cancer metabolism and could be a future target for precision medicine. A recent study revealed that in colon cancer, bacteria form polysaccharide matrices called biofilms at a high frequency in the proximal colon. Comprehensive untargeted and stable isotope-assisted metabolomic analysis revealed that the bacteria utilize polyamine metabolites produced from colon adenomas/carcinomas to build these protective biofilms and may contribute to inflammation and proliferation observed in colon cancer...
October 11, 2016: Cancer Research
Mengchao Shi, Kristopher A Kleski, Kevin R Trabbic, Jean-Paul Bourgault, Peter R Andreana
Sialyl Tn (STn) is a tumor associated carbohydrate antigen (TACA) that is overexpressed in a variety of carcinomas such as breast, ovarian and colon cancer. In normal tissue, STn is not detectable which is critical for opportunities in develop-ing cancer immunotherapies. A novel, entirely carbohydrate, semi-synthetic STn-PS A1 conjugate was prepared and eval-uated in C57BL/6 mice. STn-PS A1 was combined with commercially available monophosphoryl lipid A (MPL)-based ad-juvant and after immunization, ELISA indicated a strong immune response for inducing both anti-STn IgM/IgG antibod-ies...
October 11, 2016: Journal of the American Chemical Society
Romain Daillère, Marie Vétizou, Nadine Waldschmitt, Takahiro Yamazaki, Christophe Isnard, Vichnou Poirier-Colame, Connie P M Duong, Caroline Flament, Patricia Lepage, Maria Paula Roberti, Bertrand Routy, Nicolas Jacquelot, Lionel Apetoh, Sonia Becharef, Sylvie Rusakiewicz, Philippe Langella, Harry Sokol, Guido Kroemer, David Enot, Antoine Roux, Alexander Eggermont, Eric Tartour, Ludger Johannes, Paul-Louis Woerther, Elisabeth Chachaty, Jean-Charles Soria, Encouse Golden, Silvia Formenti, Magdalena Plebanski, Mutsa Madondo, Philip Rosenstiel, Didier Raoult, Vincent Cattoir, Ivo Gomperts Boneca, Mathias Chamaillard, Laurence Zitvogel
The efficacy of the anti-cancer immunomodulatory agent cyclophosphamide (CTX) relies on intestinal bacteria. How and which relevant bacterial species are involved in tumor immunosurveillance, and their mechanism of action are unclear. Here, we identified two bacterial species, Enterococcus hirae and Barnesiella intestinihominis that are involved during CTX therapy. Whereas E. hirae translocated from the small intestine to secondary lymphoid organs and increased the intratumoral CD8/Treg ratio, B. intestinihominis accumulated in the colon and promoted the infiltration of IFN-γ-producing γδT cells in cancer lesions...
September 28, 2016: Immunity
Rongfei Han, Guanqun Huang, Yejun Wang, Yafei Xu, Yueming Hu, Wenqi Jiang, Tianfu Wang, Tian Xiao, Duo Zheng
Gene expression in metazoans is delicately organized. As genetic information transmits from DNA to RNA and protein, expression noise is inevitably generated. Recent studies begin to unveil the mechanisms of gene expression noise control, but the changes of gene expression precision in pathologic conditions like cancers are unknown. Here we analyzed the transcriptomic data of human breast, liver, lung and colon cancers, and found that the expression noise of more than 74.9% genes was increased in cancer tissues as compared to adjacent normal tissues...
October 4, 2016: Oncotarget
Łukasz Michalak, Magdalena Bulska, Katarzyna Kudłacz, Piotr Szcześniak
Neutrophil gelatinase-associated lipocalin, known also as 24p3 lipocalin, lipocalin-2 or uterocalin (in mouse), is a small secretory protein binding small molecular weight ligands which takes part in numerous processes including apoptosis induction in leukocytes, iron transport, smell, and prostaglandins and retinol transport [19]. It was discovered in activated neutrophils as a covalent peptide associated with human gelatinase neutrophils [7]. Neutrophil lipocalin is secreted physiologically in the digestive system, respiratory tract, renal tubular cells, liver or immunity system...
January 4, 2016: Postȩpy Higieny i Medycyny Doświadczalnej
Zahra Taherian-Esfahani, Atieh Abedin-Do, Zahra Nouri, Reza Mirfakhraie, Soudeh Ghafouri-Fard, Elahe Motevaseli
BACKGROUND: Lactobacilli are a group of beneficial bacteria whose anti cancer effects have been evaluated in different cancer cell lines as well as animal models and human subjects. Such anti cancer effects can be exerted via different mechanisms such as modulation of immune response as well as inhibition of pathogens colonization. In addition, lactobacilli have direct cytotoxic effects against cancer cells which may be exerted through modulation of expression cancer related pathways...
June 2016: Iranian Journal of Cancer Prevention
Kathryn P Haley, Jennifer A Gaddy
Helicobacter pylori colonizes the stomachs of greater than 50% of the world's human population making it arguably one of the most successful bacterial pathogens. Chronic H. pylori colonization results in gastritis in nearly all patients; however in a subset of people, persistent infection with H. pylori is associated with an increased risk for more severe disease outcomes including B-cell lymphoma of mucosal-associated lymphoid tissue (MALT lymphoma) and invasive adenocarcinoma. Research aimed at elucidating determinants that mediate disease progression has revealed genetic differences in both humans and H...
2016: Gastroenterology Research and Practice
Stephanie M Wood, Anthony J Gill, Alexander S Brodsky, Shaolei Lu, Kenneth Friedman, Galina Karashchuk, Kara Lombardo, Dongfang Yang, Murray B Resnick
Fatty acid-binding protein 1 (FABP1) is an intracellular protein responsible for the transportation of long chain fatty acids. Aside from its functions in lipid metabolism and cellular differentiation, FABP1 also plays a role in inflammation through its interaction with peroxisome proliferator-activated receptors (PPARs). Previously, we compared expression of colonic epithelium genes in a subset of microsatellite instable (MSI) colorectal carcinomas (medullary carcinomas) to normal colonic mucosa and found that FABP1 expression was markedly decreased in the tumors...
September 30, 2016: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
Kaname Ohyama, Haruka Yoshimi, Nozomi Aibara, Yoichi Nakamura, Yasuyoshi Miyata, Hideki Sakai, Fumihiko Fujita, Yoshitaka Imaizumi, Anil K Chauhan, Naoya Kishikawa, Naotaka Kuroda
Cancer immunotherapies such as antibodies targeting T cell checkpoints, or adaptive tumor-infiltrating lymphocyte (TIL) transfer, have been developed to boost the endogenous immune response against human malignancies. However, activation of T cells by such antibodies can lead to the risk of autoimmune diseases. Also, the selection of tumor-reactive T cells for TIL relies on information regarding mutated antigens in tumors and does not reflect other factors involved in protein antigenicity. It is therefore essential to engineer therapeutic interventions by which T cell reactivity against tumor cells is selectively enhanced (i...
September 29, 2016: International Journal of Cancer. Journal International du Cancer
Alain P Gobert, Keith T Wilson
Helicobacter pylori is a Gram-negative bacterium that specifically colonizes the gastric ecological niche. During the infectious process, which results in diseases ranging from chronic gastritis to gastric cancer, the host response is characterized by the activation of the innate immunity of gastric epithelial cells and macrophages. These cells thus produce effector molecules such as reactive oxygen species (ROS) to counteract the infection. The generation of ROS in response to H. pylori involves two canonical pathways: 1) the NADPH-dependent reduction of molecular oxygen to generate O2(•-), which can dismute to generate ROS; and 2) the back-conversion of the polyamine spermine into spermidine through the enzyme spermine oxidase, leading to H2O2 production...
September 25, 2016: Free Radical Biology & Medicine
Ferenc Sipos, Gábor Firneisz, Györgyi Műzes
Colonic inflammation is required to heal infections, wounds, and maintain tissue homeostasis. As the seventh hallmark of cancer, however, it may affect all phases of tumor development, including tumor initiation, promotion, invasion and metastatic dissemination, and also evasion immune surveillance. Inflammation acts as a cellular stressor and may trigger DNA damage or genetic instability, and, further, chronic inflammation can provoke genetic mutations and epigenetic mechanisms that promote malignant cell transformation...
September 21, 2016: World Journal of Gastroenterology: WJG
Elham Behzadi, Raheleh Halabian, Hamideh Mahmoodzadeh Hosseini, Abbas Ali Imani Fooladi
DNA vaccination -a third generation vaccine-is a modern approach to stimulate humoral and cellular responses against different diseases such as infectious diseases, cancer and autoimmunity. These vaccines are composed of a gene that encodes sequences of a desired protein under control of a proper (eukaryotic or viral) promoter. Immune response following DNA vaccination is influenced by the route and the dose of injection. In addition, antigen presentation following DNA administration has three different mechanisms including antigen presentation by transfected myocytes, transfection of professional antigen presenting cells (APCs) and cross priming...
September 23, 2016: Microbial Pathogenesis
Tijana Borovski, Thomas T Vellinga, Jamila Laoukili, Evan E Santo, Szabolcs Fatrai, Susanne van Schelven, Andre Verheem, Dieuwke L Marvin, Inge Ubink, Inne H M Borel Rinkes, Onno Kranenburg
BACKGROUND AND AIM: Colorectal cancer (CRC) remains one of the leading causes of cancer-related death. Novel therapeutics are urgently needed, especially for tumours with activating mutations in KRAS (∼40%). Here we investigated the role of RAF1 in CRC, as a potential, novel target. METHODS: Colonosphere cultures were established from human tumour specimens obtained from patients who underwent colon or liver resection for primary or metastatic adenocarcinoma. The role of RAF1 was tested by generating knockdowns (KDs) using three independent shRNA constructs or by using RAF1-kinase inhibitor GW5074...
September 26, 2016: Gut
Pinying Shen, Rongxi Yue, Jiahong Tang, Haige Si, Liqun Shen, Changsheng Guo, Lixin Zhang, Huaizhong Han, Haihan K Song, Pengfei Zhao, Ning Wang, Zongchang Song, Chunliang Guo
While infection with H. pylori is a strong risk factor for gastric cancer, most H. pylori-colonized individuals, even those with the high-risk CagA(+)VacA(+) strain, remain asymptomatic over their lifetime. We hypothesized that the discordant outcomes were due to differences in the host immune responses. Previously, Tim-3-mediated immune modulation was observed in H. pylori-challenged mice. In this study, we compared Tim-3-related responses in CagA(+)VacA(+) H. pylori-infected asymptomatic individuals and H...
2016: American Journal of Translational Research
Eva Kristine Klemsdal Henriksen, Kristin Kaasen Jørgensen, Fatemeh Kaveh, Kristian Holm, David Hamm, Johanna Olweus, Espen Melum, Brian K Chung, Tor J Eide, Knut E A Lundin, Kirsten Muri Boberg, Tom H Karlsen, Gideon M Hirschfield, Evaggelia Liaskou
BACKGROUND & AIMS: Recruitment of gut-derived memory T cells to the liver is believed to drive hepatic inflammation in primary sclerosing cholangitis (PSC). However, whether gut-infiltrating and liver-infiltrating T cells share T-cell receptors (TCRs) and antigenic specificities is unknown. We used paired gut and liver samples from PSC patients with concurrent inflammatory bowel disease (PSC-IBD), and normal tissue samples from colon cancer controls, to assess potential T-cell clonotype overlap between the two compartments...
September 16, 2016: Journal of Hepatology
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