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Immune Colon Cancer

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https://www.readbyqxmd.com/read/28345650/rational-combination-of-oncolytic-vaccinia-virus-and-pd-l1-blockade-works-synergistically-to-enhance-therapeutic-efficacy
#1
Zuqiang Liu, Roshni Ravindranathan, Pawel Kalinski, Z Sheng Guo, David L Bartlett
Both anti-PD1/PD-L1 therapy and oncolytic virotherapy have demonstrated promise, yet have exhibited efficacy in only a small fraction of cancer patients. Here we hypothesized that an oncolytic poxvirus would attract T cells into the tumour, and induce PD-L1 expression in cancer and immune cells, leading to more susceptible targets for anti-PD-L1 immunotherapy. Our results demonstrate in colon and ovarian cancer models that an oncolytic vaccinia virus attracts effector T cells and induces PD-L1 expression on both cancer and immune cells in the tumour...
March 27, 2017: Nature Communications
https://www.readbyqxmd.com/read/28344891/tumor-infiltrating-cd39-%C3%AE-%C3%AE-tregs-are-novel-immunosuppressive-t-cells-in-human-colorectal-cancer
#2
Guoming Hu, Pin Wu, Pu Cheng, Zhigang Zhang, Zhen Wang, Xiuyan Yu, Xuan Shao, Dang Wu, Jun Ye, Tao Zhang, Xiaochen Wang, Fuming Qiu, Jun Yan, Jian Huang
Tumor microenvironment (TME) promotes immune suppression through recruiting and expanding suppressive immune cells such as regulatory T cells (Tregs) to facilitate cancer progression. In this study, we identify a novel CD39(+) γδTreg in human colorectal cancer (CRC). CD39(+) γδTregs are the predominant regulatory T cells and have more potent immunosuppressive activity than CD4(+) or CD8(+) Tregs via the adenosine-mediated pathway but independent of TGF-β or IL-10. They also secrete cytokines including IL-17A and GM-CSF, which may chemoattract myeloid-derived suppressive cells (MDSCs), thus establishing an immunosuppressive network...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28344873/a-specific-immune-and-lymphatic-profile-characterizes-the-pre-metastatic-state-of-the-sentinel-lymph-node-in-patients-with-early-cervical-cancer
#3
Cédric Balsat, Silvia Blacher, Michael Herfs, Maureen Van de Velde, Nicolas Signolle, Philippe Sauthier, Charles Pottier, Stéphanie Gofflot, Marjolein De Cuypere, Philippe Delvenne, Frédéric Goffin, Agnès Noel, Frédéric Kridelka
The lymph node (LN) pre-metastatic niche is faintly characterized in lymphophilic human neoplasia, although LN metastasis is considered as the strongest prognostic marker of patient survival. Due to its specific dissemination through a complex bilateral pelvic lymphatic system, early cervical cancer is a relevant candidate for investigating the early nodal metastatic process. In the present study, we analyzed in-depth both the lymphatic vasculature and the immune climate of pre-metastatic sentinel LN (SLN), in 48 cases of FIGO stage IB1 cervical neoplasms...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28344572/gut-colonization-by-methanogenic-archaea-is-associated-with-organic-dairy-consumption-in-children
#4
Jeroen A A van de Pol, Niels van Best, Catherine A Mbakwa, Carel Thijs, Paul H Savelkoul, Ilja C W Arts, Mathias W Hornef, Monique Mommers, John Penders
The gut microbiota represents a complex and diverse ecosystem with a profound impact on human health, promoting immune maturation, and host metabolism as well as colonization resistance. Important members that have often been disregarded are the methanogenic archaea. Methanogenic archaea reduce hydrogen levels via the production of methane, thereby stimulating food fermentation by saccharolytic bacteria. On the other hand, colonization by archaea has been suggested to promote a number of gastrointestinal and metabolic diseases such as colorectal cancer, inflammatory bowel disease, and obesity...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/28337197/hypofractionated-irradiation-has-immune-stimulatory-potential-and-induces-a-timely-restricted-infiltration-of-immune-cells-in-colon-cancer-tumors
#5
Benjamin Frey, Michael Rückert, Julia Weber, Xaver Mayr, Anja Derer, Michael Lotter, Christoph Bert, Franz Rödel, Rainer Fietkau, Udo S Gaipl
In addition to locally controlling the tumor, hypofractionated radiotherapy (RT) particularly aims to activate immune cells in the RT-modified microenvironment. Therefore, we examined whether hypofractionated RT can activate dendritic cells (DCs), induce immune cell infiltration in tumors, and how the chronology of immune cell migration into tumors occurs to gain knowledge for future definition of radiation breaks and inclusion of immunotherapy. Colorectal cancer treatments offer only limited survival benefit, and immunobiological principles for additional therapies need to be explored with preclinical models...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28331843/curative-effect-of-hf10-on-liver-and-peritoneal-metastasis-mediated-by-host-antitumor-immunity
#6
Yoshihiro Hotta, Hideki Kasuya, Itzel Bustos, Yoshinori Naoe, Toru Ichinose, Maki Tanaka, Yasuhiro Kodera
BACKGROUND: HF10 is a highly attenuated type 1 herpes simplex virus (HSV) with proven effective oncolytic effect. Previous investigations have demonstrated that colon cancer mice model treated with HF10 not only had better survival but were also resistant to the reimplantation of the antitumor effect mediated by host antitumor immunity. Importantly, it has also been noted that in mice with antitumors implanted on both sides of the back, an injection of HF10 on only one side strongly restrains not only the injected antitumor but also the non-injected ones...
2017: Oncolytic Virotherapy
https://www.readbyqxmd.com/read/28328000/cdx2-prognostic-value-in-stage-ii-iii-resected-colon-cancer-is-related-to-cms-classification
#7
C Pilati, J Taieb, R Balogoun, L Marisa, A de Reyniès, P Laurent-Puig
Caudal-type homeobox transcription factor 2 (CDX2) is involved in colon cancer (CC) oncogenesis and has been proposed as a prognostic biomarker in patients with stage II or III CC. We analyzed CDX2 expression in a series of 469 CC typed for the new international consensus molecular subtype (CMS) classification, and we confirmed results in a series of 90 CC. Here, we show that lack of CDX2 expression is only present in the mesenchymal subgroup (CMS4) and in MSI-immune tumors (CMS1) and not in CMS2 and CMS3 colon cancer...
February 27, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/28321154/host-pathogen-interactions-in-helicobacter-pylori-related-gastric-cancer
#8
EDITORIAL
Magdalena Chmiela, Zuzanna Karwowska, Weronika Gonciarz, Bujana Allushi, Paweł Stączek
Helicobacter pylori (H. pylori), discovered in 1982, is a microaerophilic, spiral-shaped gram-negative bacterium that is able to colonize the human stomach. Nearly half of the world's population is infected by this pathogen. Its ability to induce gastritis, peptic ulcers, gastric cancer and mucosa-associated lymphoid tissue lymphoma has been confirmed. The susceptibility of an individual to these clinical outcomes is multifactorial and depends on H. pylori virulence, environmental factors, the genetic susceptibility of the host and the reactivity of the host immune system...
March 7, 2017: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/28319059/camk2%C3%AE-in-intestinal-epithelial-cells-modulates-colitis-associated-colorectal-carcinogenesis-via-enhancing-stat3-activation
#9
X Ma, Z Meng, L Jin, Z Xiao, X Wang, W M Tsark, L Ding, Y Gu, J Zhang, B Kim, M He, X Gan, J E Shively, H Yu, R Xu, W Huang
Inflammation is one of the major risk factors for cancer. Here, we show that calcium/calmodulin-dependent protein kinase II gamma (CAMK2γ) in intestinal epithelial cells (IECs) modulates inflammatory signals and promotes colitis-associated cancer (CAC) in mice. We have identified CAMK2γ as a downstream target of colitis-induced WNT5A signaling. Furthermore, we have shown that CAMK2γ protects against intestine tissue injury by increasing IEC survival and proliferation. Calcium/calmodulin-dependent protein kinase II gamma knockout mice displayed reduced CAC...
March 20, 2017: Oncogene
https://www.readbyqxmd.com/read/28315775/assessment-of-histone-tail-modifications-and-transcriptional-profiling-during-colon-cancer-progression-reveals-a-global-decrease-in-h3k4me3-activity
#10
Karen Triff, Mathew W McLean, Kranti Konganti, Jiahui Pang, Evelyn Callaway, Beiyan Zhou, Ivan Ivanov, Robert S Chapkin
During colon cancer, epigenetic alterations contribute to the dysregulation of major cellular functions and signaling pathways. Modifications in chromatin signatures such as H3K4me3 and H3K9ac, which are associated with transcriptionally active genes, can lead to genomic instability and perturb the expression of gene sets associated with oncogenic processes. In order to further elucidate early pre-tumorigenic epigenetic molecular events driving CRC, we integrated diverse, genome-wide, epigenetic inputs (by high throughput sequencing of RNA, H3K4me3, and H3K9ac) and compared differentially expressed transcripts (DE) and enriched regions (DER) in an in-vivo rat colon cancer progression model...
March 15, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28303727/enhancement-of-nk-cells-proliferation-and-function-by-shikonin
#11
Yan Li, Hailin Lu, Yongchun Gu, Zhiqiang Ning, Tinghua Cao, Chao Chen, Chengru Hu, Min Tao
CONTEXT: Shikonin is a kind of naphthoquinone compound found mainly in Lithospermum erythrorhizon Sieb,et Zucc. Previous studies have shown that Shikonin has anti-tumor, anti-inflammatory and extensive pharmacological effects. According to new studies, Shikonin could also modulate the immune system function, but the effect to NK (nature killer) cells is yet unknown. OBJECTIVE: To investigate the effect and mechanism of Shikonin on NK cells proliferation and cytotoxicity to colon cancer cell line (Caco-2)...
March 17, 2017: Immunopharmacology and Immunotoxicology
https://www.readbyqxmd.com/read/28299902/when-metastasis-spns-out-of-control-coverage-of-genome-wide-in-vivo-screen-identifies-novel-host-regulators-of-metastatic-colonization
#12
Marie R Webster, Curtis H Kugel, Ashani T Weeraratna
Metastasis is the major cause of death from cancer in patients. Invasive tumor cells that leave the primary tumor must undergo a strenuous journey including extravasation, survival in the blood, intravasation into the distal site, and proliferation in a new microenvironment to form metastatic colonies. The tumor cells that are successful in forming colonies have dodged multiple perils including evading immune defenses and oxidative stress in the circulatory system. This article is protected by copyright. All rights reserved...
March 16, 2017: Pigment Cell & Melanoma Research
https://www.readbyqxmd.com/read/28296893/hnrnp-i-regulates-neonatal-immune-adaptation-and-prevents-colitis-and-colorectal-cancer
#13
Zhigang Jin, Feng Liang, Jing Yang, Wenyan Mei
The intestinal epithelium plays a critical role in host-microbe homeostasis by sensing gut microbes and subsequently initiating proper immune responses. During the neonatal stage, the intestinal epithelium is under immune repression, allowing the transition for newborns from a relatively sterile intra-uterine environment to one that is rich in foreign antigens. The mechanism underlying such immune repression remains largely unclear, but involves downregulation of IRAK1 (interleukin-1 receptor-associated kinase), an essential component of toll-like receptor-mediated NF-κB signaling...
March 15, 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28287848/immunomodulating-and-immunoresistance-properties-of-cancer-initiating-cells-implications-for-the-clinical-success-of-immunotherapy
#14
Cristina Maccalli, Giorgio Parmiani, Soldano Ferrone
Cancer-initiating cells (CICs) represent a relatively rare subpopulation of cells endowed with self-renewal, stemness properties, tumorigenicity in immunodeficient mice, and resistance to standard therapies as well as to immunotherapy. Here, we review the biological and immunological characteristics of CICs with special focus on the immunomodulating mechanisms they utilize to escape from immunosurveillance. The recently developed immunotherapeutic strategies have yielded remarkable clinical results in many types of tumors, indicating that indeed a patient's immune system can mount an immune response, which is effective in controlling tumor growth...
March 13, 2017: Immunological Investigations
https://www.readbyqxmd.com/read/28280601/minimal-residual-disease-in-melanoma-circulating-melanoma-cells-and-predictive-role-of-mcam-muc18-melcam-cd146
#15
REVIEW
Maria Cristina Rapanotti, Elena Campione, Giulia Spallone, Augusto Orlandi, Sergio Bernardini, Luca Bianchi
Circulating tumour cells (CTCs), identified in numerous cancers including melanoma, are unquestionably considered valuable and useful as diagnostic and prognostic markers. They can be detected at all melanoma stages and may persist long after treatment. A crucial step in metastatic processes is the intravascular invasion of neoplastic cells as circulating melanoma cells (CMCs). Only a small percentage of these released cells are efficient and capable of colonizing with a strong metastatic potential. CMCs' ability to survive in circulation express a variety of genes with continuous changes of signal pathways and proteins to escape immune surveillance...
2017: Cell Death Discovery
https://www.readbyqxmd.com/read/28278498/hypoxia-enhances-immunosuppression-by-inhibiting-cd4-effector-t-cell-function-and-promoting-treg-activity
#16
Astrid M Westendorf, Kathrin Skibbe, Alexandra Adamczyk, Jan Buer, Robert Geffers, Wiebke Hansen, Eva Pastille, Verena Jendrossek
BACKGROUND/AIMS: Hypoxia occurs in many pathological conditions, including inflammation and cancer. Within this context, hypoxia was shown to inhibit but also to promote T cell responses. Due to this controversial function, we aimed to explore whether an insufficient anti-tumour response during colitis-associated colon cancer could be ascribed to a hypoxic microenvironment. METHODS: Colitis-associated colon cancer was induced in wildtype mice, and hypoxia as well as T cell immunity were analysed in the colonic tumour tissues...
March 8, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28278221/antitumor-activity-of-orally-administered-maitake-%C3%AE-glucan-by-stimulating-antitumor-immune-response-in-murine-tumor
#17
Yuki Masuda, Yoshiaki Nakayama, Akihiro Tanaka, Kenta Naito, Morichika Konishi
Maitake α-glucan, YM-2A, isolated from Grifola frondosa, has been characterized as a highly α-1,6-branched α-1,4 glucan. YM-2A has been shown to possess an anti-virus effect in mice; however, it does not directly inhibit growth of the virus in vitro, indicating that the anti-virus effect of YM-2A might be associated with modulation of the host immune system. In this study, we found that oral administration of YM-2A could inhibit tumor growth and improve survival rate in two distinct mouse models of colon-26 carcinoma and B16 melanoma...
2017: PloS One
https://www.readbyqxmd.com/read/28278128/cancer-metastasis-tricks-of-the-trade
#18
REVIEW
Rabia Zeeshan, Zeeshan Mutahir
Decades of cancer research have unraveled genetic, epigenetic and molecular pathways leading to plausible therapeutic targets; many of which hold great promise in improving clinical outcomes. Metastatic tumors become evident early on and are one of the major causes of cancer-related fatalities worldwide. This review depicts the sequential events of cancer metastasis. Genetic and epigenetic heterogeneity influences local tumor cell invasion, intravasation, survival in circulation, extravasation and colonization to distant sites...
March 9, 2017: Bosnian Journal of Basic Medical Sciences
https://www.readbyqxmd.com/read/28275039/right-versus-left-colon-cancer-biology-integrating-the-consensus-molecular-subtypes
#19
REVIEW
Michael S Lee, David G Menter, Scott Kopetz
Although clinical management of colon cancer generally has not accounted for the primary tumor site, left-sided and right-sided colon cancers harbor different clinical and biologic characteristics. Right-sided colon cancers are more likely to have genome-wide hypermethylation via the CpG island methylator phenotype (CIMP), hypermutated state via microsatellite instability, and BRAF mutation. There are also differential exposures to potential carcinogenic toxins and microbiota in the right and left colon. Gene expression analyses further shed light on distinct biologic subtypes of colorectal cancers (CRCs), with 4 consensus molecular subtypes (CMSs) identified...
March 2017: Journal of the National Comprehensive Cancer Network: JNCCN
https://www.readbyqxmd.com/read/28258220/adiponectin-confers-protection-from-acute-colitis-and-restricts-a-b-cell-immune-response
#20
Stephanie Obeid, Miriam Wankell, Berenice Charrez, Jade Sternberg, Roxane Kreuter, Saeed Esmaili, Mehdi Ramezani-Moghadam, Carol Devine, Scott Read, Prithi Bhathal, Andreas Lopata, Golo Ahlenstiel, Liang Qiao, Jacob George, Lionel Hebbard
Adiponectin demonstrates beneficial effects in various metabolic diseases including diabetes, and in bowel cancer. Recent data also suggests a protective role in colitis. However, the precise molecular mechanisms by which adiponectin and its receptors modulate colitis and the nature of the adaptive immune response in murine models are yet to be elucidated. Adiponectin-knockout mice were orally administered dextran sulfate sodium for 7 days, and were compared to wild-type mice. The severity of disease was analysed histopathologically, and through cytokine profiling...
March 3, 2017: Journal of Biological Chemistry
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