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Tumor immune recognition

Erika Heninger, Timothy E G Krueger, Stephanie M Thiede, Jamie M Sperger, Brianna L Byers, Madison R Kircher, David Kosoff, Bing Yang, David F Jarrard, Douglas G McNeel, Joshua M Lang
Immune tolerance to self-antigens can limit robust anti-tumor immune responses in the use of tumor vaccines. Expression of novel tumor associated antigens can improve immune recognition and lysis of tumor cells. The cancer-testis antigen (CTA) family of proteins has been hypothesized to be an ideal class of antigens due to tumor-restricted expression, a subset of which have been found to induce antibody responses in patients with prostate disease. We demonstrate that CTA expression is highly inducible in five different Prostate Cancer (PC) cell lines using a hypomethylating agent 5-Aza-2'-deoxycytidine (5AZA) and/or a histone deacetylase inhibitor LBH589...
October 17, 2016: Oncotarget
Camille Detree, Gustavo Núñez-Acuña, Steven Roberts, Cristian Gallardo-Escárate
Saxitoxin (STX), a principal phycotoxin contributing to paralytic shellfish poisoning, is largely produced by marine microalgae of the genus Alexandrium. This toxin affects a wide range of species, inducing massive deaths in fish and other marine species. However, marine bivalves can resist and accumulate paralytic shellfish poisons. Despite numerous studies on the impact of STX in marine bivalves, knowledge regarding STX recognition at molecular level by benthic species remains scarce. Therefore, the aim of this study was to identify novel genes that interact with STX in the Chilean mussel Mytilus chilensis...
2016: PloS One
Sarah A Weiss, Joseph Han, Farbod Darvishian, Jeremy Tchack, Sung Won Han, Karolina Malecek, Michelle Krogsgaard, Iman Osman, Judy Zhong
BACKGROUND: Age has been reported as an independent prognostic factor for melanoma-specific survival (MSS). We tested the hypothesis that age impacts the host anti-tumor immune response, accounting for age-specific survival outcomes in three unique melanoma patient cohorts. METHODS: We queried the U.S. population-based Surveillance, Epidemiology, and End Results Program (SEER), the prospective tertiary care hospital-based Interdisciplinary Melanoma Cooperative Group (IMCG) biorepository, and the Cancer Genome Atlas (TCGA) biospecimen database to test the association of patient age at time of melanoma diagnosis with clinicopathologic features and survival outcomes...
October 19, 2016: Journal of Translational Medicine
Raphaela Mayerhofer, Esther E Fröhlich, Florian Reichmann, Aitak Farzi, Nora Kogelnik, Eleonore Fröhlich, Wolfgang Sattler, Peter Holzer
Microbial metabolites are known to affect immune system, brain, and behavior via activation of pattern recognition receptors such as Toll-like receptor 4 (TLR4). Unlike the effect of the TLR4 agonist lipopolysaccharide (LPS), the role of other TLR agonists in immune-brain communication is insufficiently understood. We therefore hypothesized that the TLR2 agonist lipoteichoic acid (LTA) causes immune activation in the periphery and brain, stimulates the hypothalamic-pituitary-adrenal (HPA) axis and has an adverse effect on blood-brain barrier (BBB) and emotional behavior...
October 14, 2016: Brain, Behavior, and Immunity
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
Anna E Kersh, Maiko Sasaki, Lee A Cooper, Haydn T Kissick, Brian P Pollack
Advances in molecular pathology have changed the landscape of oncology. The ability to interrogate tissue samples for oncogene amplification, driver mutations, and other molecular alterations provides clinicians with an enormous level of detail about their patient's cancer. In some cases, this information informs treatment decisions, especially those related to targeted anti-cancer therapies. However, in terms of immune-based therapies, it is less clear how to use such information. Likewise, despite studies demonstrating the pivotal role of neoantigens in predicting responsiveness to immune checkpoint blockade, it is not known if the expression of neoantigens impacts the response to targeted therapies despite a growing recognition of their diverse effects on immunity...
2016: Frontiers in Pharmacology
Martin Böhland, Eugenia Kress, Matthias B Stope, Thomas Pufe, Simone C Tauber, Lars-Ove Brandenburg
Bacterial meningitis is - despite therapeutical progress during the last decades - still characterized by high mortality and severe permanent neurogical sequelae. The brain is protected from penetrating pathogens by both the blood-brain barrier and the innate immune system. Invading pathogens are recognized by so-called pattern recognition receptors including the Toll-like receptors (TLR) which are expressed by glial immune cells in the central nervous system. Among these, TLR2 is responsible for the detection of Gram-positive bacteria such as the meningitis-causing pathogen Streptococcus pneumoniae...
October 15, 2016: Journal of Neuroimmunology
Kirsteen M Tullett, Ingrid M Leal Rojas, Yoshihito Minoda, Peck S Tan, Jian-Guo Zhang, Corey Smith, Rajiv Khanna, Ken Shortman, Irina Caminschi, Mireille H Lahoud, Kristen J Radford
DC-based vaccines that initiate T cell responses are well tolerated and have demonstrated efficacy for tumor immunotherapy, with the potential to be combined with other therapies. Targeting vaccine antigens (Ag) directly to the DCs in vivo is more effective than cell-based therapies in mouse models and is therefore a promising strategy to translate to humans. The human CD141(+) DCs are considered the most clinically relevant for initiating CD8(+) T cell responses critical for killing tumors or infected cells, and they specifically express the C-type lectin-like receptor CLEC9A that facilitates presentation of Ag by these DCs...
May 19, 2016: JCI Insight
Kole T Roybal, Jasper Z Williams, Leonardo Morsut, Levi J Rupp, Isabel Kolinko, Joseph H Choe, Whitney J Walker, Krista A McNally, Wendell A Lim
Redirecting T cells to attack cancer using engineered chimeric receptors provides powerful new therapeutic capabilities. However, the effectiveness of therapeutic T cells is constrained by the endogenous T cell response: certain facets of natural response programs can be toxic, whereas other responses, such as the ability to overcome tumor immunosuppression, are absent. Thus, the efficacy and safety of therapeutic cells could be improved if we could custom sculpt immune cell responses. Synthetic Notch (synNotch) receptors induce transcriptional activation in response to recognition of user-specified antigens...
October 6, 2016: Cell
Yuwei Chenzhang, Qiang Wen, Xianping Ding, Man Cao, Zuyi Chen, Xuemei Mu, Tao Wang
Cervical cancers almost are infected by human papillmavirus (HPV), encoding E6 and E7 oncoproteins which are regard as ideal targets on the mechanism of this disease and development of vaccines. HLA (human leukocyte antigen) participates in the local immune response to prevent tumor invasion and progression. But due to highly polymorphism of HLA, prediction shows its importance in this study. More effective immunoinformatics was used for predicting epitopes from HPV-16 E6 and E7, including T- and B-cell epitopes...
September 27, 2016: Immunology Letters
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
Sheila López-Cobo, Carmen Campos-Silva, Mar Valés-Gómez
Communication within the immune system depends on the release of factors that can travel and transmit information at points distant from the cell that produced them. In general, immune cells use two key strategies that can occur either at the plasma membrane or in intracellular compartments to produce such factors, vesicle release and proteolytic cleavage. Release of soluble factors in exosomes, a subset of vesicles that originate from intracellular compartments, depends generally on biochemical and lipid environment features...
2016: Frontiers in Cell and Developmental Biology
B Seliger
Although the human immune system can recognize and eradicate tumor cells, tumors have also been shown to develop different strategies to escape immune surveillance, which has been described for the first time in different mouse models. The evasion of immune recognition was often associated with a poor prognosis and reduced survival of patients. During the last years the molecular mechanisms, which protect tumor cells from this immune attack, have been identified and appear to be more complex than initially expected...
November 2016: HLA
Fabio Morandi, Roberta Rizzo, Enrico Fainardi, Nathalie Rouas-Freiss, Vito Pistoia
HLA-G is a HLA-class Ib molecule with potent immunomodulatory activities, which is expressed in physiological conditions, where modulation of the immune response is required to avoid allograft recognition (i.e., maternal-fetal interface or transplanted patients). However, HLA-G can be expressed de novo at high levels in several pathological conditions, including solid and hematological tumors and during microbial or viral infections, leading to the impairment of the immune response against tumor cells or pathogens, respectively...
2016: Journal of Immunology Research
Bai Liu, Lin Kong, Kaiping Han, Hao Hong, Warren D Marcus, Xiaoyue Chen, Emily K Jeng, Sarah Alter, Xiaoyun Zhu, Mark P Rubinstein, Sixiang Shi, Peter R Rhode, Weibo Cai, Hing C Wong
Interleukin (IL)-15 and its receptor α (IL-15Rα) are co-expressed on antigen-presenting cells allowing transpresentation of IL-15 to immune cells bearing IL-2RβγC and stimulation of effector immune responses. We previously reported that the high-affinity interactions between an IL-15 superagonist (IL-15N72D) and the extracellular IL-15Rα sushi domain (IL-15RαSu) could be exploited to create a functional scaffold for the design of multivalent disease-targeted complexes. The IL-15N72D/IL-15RαSuFc complex, also known as ALT-803, is a multimeric complex constructed by fusing IL-15N72D/IL-15RαSu to the Fc-domain of IgG1...
September 20, 2016: Journal of Biological Chemistry
Yan-Xin Ren, Jie Yang, Rui-Mei Sun, Li-Juan Zhang, Liu-Fang Zhao, Bao-Zhong Li, Lei Li, Hai-Ting Long, Qiang-Ming Sun, Yun-Chao Huang, Xiao-Jiang Li
The HLA-I antigen processing machinery (APM) plays a crucial role in the anticancer immune response. The loss of surface expression of HLA-I molecules is particularly important as this enables tumor cells to evade recognition and lysis by cytotoxic T-lymphocytes. Transcriptional control of the APM genes is regulated by the nuclear factor kappa B (NF-κB). BCRFl is an Epstein-Barr virus homologue of human IL-10 (hIL-10) and is known as viral IL-10 (vIL-10). vIL-10 shares many immunosuppressive effects with hIL-10 but lacks the immunostimulatory effect of hIL-10...
September 20, 2016: Cytotechnology
Qi Chen, Lijun Sun, Zhijian J Chen
The recognition of microbial nucleic acids is a major mechanism by which the immune system detects pathogens. Cyclic GMP-AMP (cGAMP) synthase (cGAS) is a cytosolic DNA sensor that activates innate immune responses through production of the second messenger cGAMP, which activates the adaptor STING. The cGAS-STING pathway not only mediates protective immune defense against infection by a large variety of DNA-containing pathogens but also detects tumor-derived DNA and generates intrinsic antitumor immunity. However, aberrant activation of the cGAS pathway by self DNA can also lead to autoimmune and inflammatory disease...
September 20, 2016: Nature Immunology
Eliza L S Fong, Daniel A Harrington, Mary C Farach-Carson, Hanry Yu
Numerous studies to date have contributed to a paradigm shift in modeling cancer, moving from the traditional two-dimensional culture system to three-dimensional (3D) culture systems for cancer cell culture. This led to the inception of tumor engineering, which has undergone rapid advances over the years. In line with the recognition that tumors are not merely masses of proliferating cancer cells but rather, highly complex tissues consisting of a dynamic extracellular matrix together with stromal, immune and endothelial cells, significant efforts have been made to better recapitulate the tumor microenvironment in 3D...
November 2016: Biomaterials
Mari Hirvinen, Cristian Capasso, Kilian Guse, Mariangela Garofalo, Andrea Vitale, Marko Ahonen, Lukasz Kuryk, Markus Vähä-Koskela, Akseli Hemminki, Vittorio Fortino, Dario Greco, Vincenzo Cerullo
In oncolytic virotherapy, the ability of the virus to activate the immune system is a key attribute with regard to long-term antitumor effects. Vaccinia viruses bear one of the strongest oncolytic activities among all oncolytic viruses. However, its capacity for stimulation of antitumor immunity is not optimal, mainly due to its immunosuppressive nature. To overcome this problem, we developed an oncolytic VV that expresses intracellular pattern recognition receptor DNA-dependent activator of IFN-regulatory factors (DAI) to boost the innate immune system and to activate adaptive immune cells in the tumor...
2016: Molecular Therapy Oncolytics
Steve Boudewijns, Kalijn F Bol, Gerty Schreibelt, Harm Westdorp, Johannes C Textor, Michelle M van Rossum, Nicole M Scharenborg, Annemiek J de Boer, Mandy W M M van de Rakt, Jeanne M Pots, Tom G M van Oorschot, Tjitske Duiveman-de Boer, Michel A Olde Nordkamp, Wilmy S E C van Meeteren, Winette T A van der Graaf, Johannes J Bonenkamp, Johannes H W de Wilt, Erik H J G Aarntzen, Cornelis J A Punt, Winald R Gerritsen, Carl G Figdor, I Jolanda M de Vries
PURPOSE: To determine the effectiveness of adjuvant dendritic cell (DC) vaccination to induce tumor-specific immunological responses in stage III melanoma patients. EXPERIMENTAL DESIGN: Retrospective analysis of stage III melanoma patients, vaccinated with autologous monocyte-derived DC loaded with tumor-associated antigens (TAA) gp100 and tyrosinase after radical lymph node dissection. Skin-test infiltrating lymphocytes (SKILs) obtained from delayed-type hypersensitivity skin-test biopsies were analyzed for the presence of TAA-specific CD8(+) T cells by tetrameric MHC-peptide complexes and by functional TAA-specific T cell assays, defined by peptide-recognition (T2 cells) and/or tumor-recognition (BLM and/or MEL624) with specific production of Th1 cytokines and no Th2 cytokines...
July 2016: Oncoimmunology
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