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Tumor immune recognition

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https://www.readbyqxmd.com/read/27906678/humoral-immune-responses-toward-tumor-derived-antigens-in-previously-untreated-patients-with-chronic-lymphocytic-leukemia
#1
Valentina Griggio, Giorgia Mandili, Candida Vitale, Michela Capello, Paolo Macor, Sara Serra, Barbara Castella, Silvia Peola, Myriam Foglietta, Daniela Drandi, Paola Omedé, Daniele Sblattero, Paola Cappello, Roberto Chiarle, Silvia Deaglio, Mario Boccadoro, Francesco Novelli, Massimo Massaia, Marta Coscia
In chronic lymphocytic leukemia (CLL) the occurrence and the impact of antibody responses toward tumor-derived antigens are largely unexplored. Our serological proteomic data show that antibodies toward 47 identified antigens are detectable in 29 out of 35 patients (83%) with untreated CLL. The glycolytic enzyme alpha-enolase (ENO1) is the most frequently recognized antigen (i.e. 54% of CLL sera). We show that ENO1 is upregulated in the proliferating B-cell fraction of CLL lymph nodes. In CLL cells of the peripheral blood, ENO1 is exclusively expressed at the intracellular level, whereas it is exposed on the surface of apoptotic leukemic cells...
November 30, 2016: Oncotarget
https://www.readbyqxmd.com/read/27893434/neuroinflammatory-and-cognitive-consequences-of-combined-radiation-and-immunotherapy-in-a-novel-preclinical-model
#2
Gwendolyn J McGinnis, David Friedman, Kristina H Young, Eileen Ruth S Torres, Charles R Thomas, Michael J Gough, Jacob Raber
BACKGROUND: Cancer patients often report behavioral and cognitive changes following cancer treatment. These effects can be seen in patients who have not yet received treatment or have received only peripheral (non-brain) irradiation. Novel treatments combining radiotherapy (RT) and immunotherapy (IT) demonstrate remarkable efficacy with respect to tumor outcomes by enhancing the proinflammatory environment in the tumor. However, a proinflammatory environment in the brain mediates cognitive impairments in other neurological disorders and may affect brain function in cancer patients receiving these novel treatments...
November 24, 2016: Oncotarget
https://www.readbyqxmd.com/read/27890174/immune-related-adverse-effects-of-cancer-immunotherapy-implications-for-rheumatology
#3
REVIEW
Laura C Cappelli, Ami A Shah, Clifton O Bingham
Immune checkpoint inhibitors (ICIs) are increasingly studied and used as therapy for a growing number of malignancies. ICIs work by blocking inhibitory pathways of T-cell activation, leading to an immune response directed against tumors. Such nonspecific immunologic activation can lead to immune-related adverse events (IRAEs). Some IRAEs, including inflammatory arthritis, sicca syndrome, myositis, and vasculitis, are of special interest to rheumatologists. As use of ICIs increases, recognition of these IRAEs and developing treatment strategies will become important...
February 2017: Rheumatic Diseases Clinics of North America
https://www.readbyqxmd.com/read/27882334/crosstalk-between-innate-lymphoid-cells-and-other-immune-cells-in-the-tumor-microenvironment
#4
REVIEW
Fabian Flores-Borja, Sheeba Irshad, Peter Gordon, Felix Wong, Ibrahim Sheriff, Andrew Tutt, Tony Ng
Our knowledge and understanding of the tumor microenvironment (TME) have been recently expanded with the recognition of the important role of innate lymphoid cells (ILC). Three different groups of ILC have been described based on their ability to produce cytokines that mediate the interactions between innate and adaptive immune cells in a variety of immune responses in infection, allergy, and autoimmunity. However, recent evidence from experimental models and clinical studies has demonstrated that ILC contribute to the mechanisms that generate suppressive or tolerant environments that allow tumor regression or progression...
2016: Journal of Immunology Research
https://www.readbyqxmd.com/read/27867386/immune-regulation-by-pericytes-modulating-innate-and-adaptive-immunity
#5
REVIEW
Rocío Navarro, Marta Compte, Luis Álvarez-Vallina, Laura Sanz
Pericytes (PC) are mural cells that surround endothelial cells in small blood vessels. PC have traditionally been credited with structural functions, being essential for vessel maturation and stabilization. However, an accumulating body of evidence suggests that PC also display immune properties. They can respond to a series of pro-inflammatory stimuli and are able to sense different types of danger due to their expression of functional pattern-recognition receptors, contributing to the onset of innate immune responses...
2016: Frontiers in Immunology
https://www.readbyqxmd.com/read/27865176/adoptive-immunotherapy-for-hematological-malignancies-current-status-and-new-insights-in-chimeric-antigen-receptor-t-cells
#6
REVIEW
Alessandro Allegra, Vanessa Innao, Demetrio Gerace, Doriana Vaddinelli, Caterina Musolino
Hematological malignancies frequently express cancer-associated antigens that are shared with normal cells. Such tumor cells elude the host immune system because several T cells targeted against self-antigens are removed during thymic development, and those that persist are eliminated by a regulatory population of T cells. Chimeric antigen receptor-modified T cells (CAR-Ts) have emerged as a novel modality for tumor immunotherapy due to their powerful efficacy against tumor cells. These cells are created by transducing genes-coding fusion proteins of tumor antigen-recognition single-chain Fv connected to the intracellular signaling domains of T cell receptors, and are classed as first-, second- and third-generation, differing on the intracellular signaling domain number of T cell receptors...
November 2016: Blood Cells, Molecules & Diseases
https://www.readbyqxmd.com/read/27859479/diverse-types-of-dermatologic-toxicities-from-immune-checkpoint-blockade-therapy
#7
REVIEW
Jonathan L Curry, Michael T Tetzlaff, Priyadharsini Nagarajan, Carol Drucker, Adi Diab, Sharon R Hymes, Madeleine Duvic, Wen-Jen Hwu, Jennifer A Wargo, Carlos A Torres-Cabala, Ronald P Rapini, Victor G Prieto
Immunomodulatory drugs that leverages host immune mechanisms to destroy tumor cells has been met with great promise in the treatment of cancer. Immunotherapy, targeting cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) and the programmed cell death 1 (PD-1) receptor and its ligand (PD-L1) have shown tremendous improvements in the survival of patients with advanced solid tumors. However, the development of dermatologic toxicity (DT) is a consequence to immunotherapy. Review of published reports of the DT to immunotherapy revealed patients receiving anti-CTCLA-4 antibody or anti-PD-1/PD-L1 antibody often develop a DT of any type and grade...
November 10, 2016: Journal of Cutaneous Pathology
https://www.readbyqxmd.com/read/27853638/natural-killer-cell-recognition-of-in-vivo-drug-induced-senescent-multiple-myeloma-cells
#8
Fabrizio Antonangeli, Alessandra Soriani, Biancamaria Ricci, Andrea Ponzetta, Giorgia Benigni, Stefania Morrone, Giovanni Bernardini, Angela Santoni
Recognition of tumor cells by the immune system is a key step in cancer eradication. Melphalan is an alkylating agent routinely used in the treatment of patients with multiple myeloma (MM), but at therapeutic doses it leads to an immunosuppressive state due to lymphopenia. Here, we used a mouse model of MM to investigate the ability of in vivo treatment with low doses of melphalan to modulate natural killer (NK) cell activity, which have been shown to play a major role in the control of MM growth. Melphalan treatment was able to enhance the surface expression of the stress-induced NKG2D ligands RAE-1 and MULT-1, and of the DNAM-1 ligand PVR (CD155) on MM cells, leading to better tumor cell recognition and killing by NK cells, as highlighted by NK cell increased degranulation triggered by melphalan-treated tumor cells...
2016: Oncoimmunology
https://www.readbyqxmd.com/read/27849169/mechanisms-of-acute-toxicity-in-nkg2d-chimeric-antigen-receptor-t-cell-treated-mice
#9
Marie-Louise Sentman, Joana M Murad, W James Cook, Ming-Ru Wu, Jake Reder, Susanne H Baumeister, Glenn Dranoff, Michael W Fanger, Charles L Sentman
Targeting cancer through the use of effector T cells bearing chimeric Ag receptors (CARs) leads to elimination of tumors in animals and patients, but recognition of normal cells or excessive activation can result in significant toxicity and even death. CAR T cells based on modified NKG2D receptors are effective against many types of tumors, and their efficacy is mediated through direct cytotoxicity and cytokine production. Under certain conditions, their ligands can be expressed on nontumor cells, so a better understanding of the potential off-tumor activity of these NKG2D CAR T cells is needed...
December 15, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/27847783/combination-approaches-with-immune-checkpoint-blockade-in-cancer-therapy
#10
REVIEW
Maarten Swart, Inge Verbrugge, Joost B Beltman
In healthy individuals, immune-checkpoint molecules prevent autoimmune responses and limit immune cell-mediated tissue damage. Tumors frequently exploit these molecules to evade eradication by the immune system. Over the past years, immune-checkpoint blockade of cytotoxic T lymphocyte antigen-4 and programed death-1 emerged as promising strategies to activate antitumor cytotoxic T cell responses. Although complete regression and long-term survival is achieved in some patients, not all patients respond. This review describes promising, novel combination approaches involving immune-checkpoint blockade in the context of the cancer-immunity cycle, aimed at increasing response rates to the single treatments...
2016: Frontiers in Oncology
https://www.readbyqxmd.com/read/27846724/-the-role-of-pd-1-pd-l1-signaling-pathway-in-antitumor-immune-response
#11
P Zatloukalová, M Pjechová, S Babčanová, T R Hupp, B Vojtěšek
BACKGROUND: Correct function of the immune system depends on close cooperation between stimulation and inhibition signals, which protect an organism from outside microorganisms and other agents, but also protects healthy tissues against possible self-destructing attacks of the immune system. However, the inhibitory mechanisms can be abused by cancer cells that evade immune responses and, in fact, they help develop cancer. Therefore, one of the characteristics of cancer cells is the ability to evade immune recognition...
2016: Klinická Onkologie: Casopis Ceské a Slovenské Onkologické Spolecnosti
https://www.readbyqxmd.com/read/27837020/density-of-immunogenic-antigens-does-not-explain-the-presence-or-absence-of-the-t-cell-inflamed-tumor-microenvironment-in-melanoma
#12
Stefani Spranger, Jason J Luke, Riyue Bao, Yuanyuan Zha, Kyle M Hernandez, Yan Li, Alexander P Gajewski, Jorge Andrade, Thomas F Gajewski
Melanoma metastases can be categorized by gene expression for the presence of a T-cell-inflamed tumor microenvironment, which correlates with clinical efficacy of immunotherapies. T cells frequently recognize mutational antigens corresponding to nonsynonymous somatic mutations (NSSMs), and in some cases shared differentiation or cancer-testis antigens. Therapies are being pursued to trigger immune infiltration into non-T-cell-inflamed tumors in the hope of rendering them immunotherapy responsive. However, whether those tumors express antigens capable of T-cell recognition has not been explored...
November 29, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27836246/emerging-role-of-immunotherapy-in-urothelial-carcinoma-immunobiology-biomarkers
#13
REVIEW
Randy F Sweis, Matthew D Galsky
Urothelial bladder cancer is one of the first cancers recognized to be immunogenic since 40 years ago when the use of bacillus Calmette-Guerin was shown to prevent recurrence. Since that time, our knowledge of immune biology of cancer has expanded tremendously, and patients with bladder cancer finally have new active immunotherapeutic drugs on the horizon. Anti-programmed cell death-1 (PD-1)/programmed cell death ligand-1 (PD-L1) therapy has shown impressively durable responses in urothelial bladder cancer (UBC), but the reported response rates warrant improvement...
December 2016: Urologic Oncology
https://www.readbyqxmd.com/read/27835902/squamous-cell-carcinomas-escape-immune-surveillance-via-inducing-chronic-activation-and-exhaustion-of-cd8-t-cells-co-expressing-pd-1-and-lag-3-inhibitory-receptors
#14
Ameet K Mishra, Tanya Kadoishi, Xiaoguang Wang, Emily Driver, Zhangguo Chen, Xiao-Jing Wang, Jing H Wang
Squamous cell carcinoma (SCC) is the second commonest type of skin cancer. Moreover, about 90% of head and neck cancers are SCCs. SCCs develop at a significantly higher rate under chronic immunosuppressive conditions, implicating a role of immune surveillance in controlling SCCs. It remains largely unknown how SCCs evade immune recognition. Here, we established a mouse model by injecting tumor cells derived from primary SCCs harboring KrasG12D mutation and Smad4 deletion into wild-type (wt) or CD8-/- recipients...
November 9, 2016: Oncotarget
https://www.readbyqxmd.com/read/27823560/redox-active-selenium-in-health-and-disease-a-conceptual-review
#15
Boguslaw Lipinski
Although it is generally accepted that selenium (Se) is important for life, it is not well known which forms of organic and/or inorganic Se compound are the most biologically active. In nature Se exists mostly in two forms, namely as selenite with fourvalent and selenate with sixvalent cations, from which all other inorganic and organic species are derived. Despite a small difference in their electronic structure, these two inorganic parent compounds differ significantly in their redox properties. Hence, only selenite can act as an oxidant, particularly in the reaction with free and/or protein-bound sulhydryl (SH) groups...
November 4, 2016: Mini Reviews in Medicinal Chemistry
https://www.readbyqxmd.com/read/27821498/established-t-cell-inflamed-tumors-rejected-after-adaptive-resistance-was-reversed-by-combination-sting-activation-and-pd-1-pathway-blockade
#16
Ellen Moore, Paul E Clavijo, Ruth Davis, Harrison Cash, Carter Van Waes, Young Kim, Clint Allen
Patients with head and neck squamous cell carcinoma harbor T cell-inflamed and non-T cell-inflamed tumors. Despite this, only 20% of patients respond to checkpoint inhibitor immunotherapy. Lack of induction of innate immunity through pattern-recognition receptors, such as the stimulator of interferon (IFN) genes (STING) receptor, may represent a significant barrier to the development of effective antitumor immunity. Here, we demonstrate robust control of a T cell-inflamed (MOC1), but not non-T cell-inflamed (MOC2), model of head and neck cancer by activation of the STING pathway with the synthetic cyclic dinucleotide RP,RP dithio-c-di-GMP...
December 2016: Cancer Immunology Research
https://www.readbyqxmd.com/read/27817214/antibody-therapeutics-for-treating-prostate-cancer-where-are-we-now-and-what-comes-next
#17
Panagiotis J Vlachostergios, Giuseppe Galletti, Jessica Palmer, Linda Lam, Beerinder S Karir, Scott T Tagawa
Progress in the understanding of molecular events of carcinogenesis and cancer evolution as well as the identification of tumor antigens has led to the development of different targeted therapeutic approaches, including the use of monoclonal antibodies (mAbs). Prostate cancer (PC) is highly amenable to mAb targeting given the existence of prostate-specific targets and the natural history and localization of metastatic disease. Areas covered: Several aspects of the PC phenotype, including growth factors, angiogenesis mediators, bone microenvironment signals, and immune evasion pathways, have become areas of ongoing investigation in terms of mAb targeting...
November 20, 2016: Expert Opinion on Biological Therapy
https://www.readbyqxmd.com/read/27814372/decreased-expression-of-tmem173-predicts-poor-prognosis-in-patients-with-hepatocellular-carcinoma
#18
Yang Bu, Fang Liu, Qing-An Jia, Song-Ning Yu
Hepatocellular carcinoma (HCC) is one of the most lethal cancer types, and chronic infection with Hepatitis B Virus (HBV) is identified as the strongest risk factor for HCC. Transmembrane Protein 173 (TMEM173) is a pattern recognition receptor which functions as a major regulator of the innate immune response to viral and bacterial infections. However, the prognostic value of TMEM173 in HCC remains elusive. Thus, we aimed to evaluate the potential prognostic significance of TMEM173 expression in HCC patients following curative resection...
2016: PloS One
https://www.readbyqxmd.com/read/27806260/crystal-structure-of-the-complex-of-human-fasl-and-its-decoy-receptor-dcr3
#19
Weifeng Liu, Udupi Ramagopal, Huiyong Cheng, Jeffrey B Bonanno, Rafael Toro, Rahul Bhosle, Chenyang Zhan, Steven C Almo
The apoptotic effect of FasL:Fas signaling is disrupted by DcR3, a unique secreted member of the tumor necrosis factor receptor superfamily, which also binds and neutralizes TL1A and LIGHT. DcR3 is highly elevated in patients with various tumors and contributes to mechanisms by which tumor cells to evade host immune surveillance. Here we report the crystal structure of FasL in complex with DcR3. Comparison of FasL:DcR3 structure with our earlier TL1A:DcR3 and LIGHT:DcR3 structures supports a paradigm involving the recognition of invariant main-chain and conserved side-chain functionalities, which is responsible for the recognition of multiple TNF ligands exhibited by DcR3...
November 1, 2016: Structure
https://www.readbyqxmd.com/read/27803458/cell-type-specific-responses-of-peripheral-blood-cd14-positive-monocytes-to-liposome-encapsulated-immunostimulatory-sirna
#20
Yasuhiro Abe, Kumiko Sakai-Kato, Yukihiro Goda
RNA interference via small interfering RNA (siRNA) has many potential therapeutic applications, and liposomal-based systems are useful for improving the pharmacokinetics of siRNAs, including their intracellular release and distribution. However, for the successful translation of this technology into clinical applications, it is important to understand how liposomal encapsulation changes the cellular uptake and immunostimulatory adverse effects of siRNAs. Here we evaluated the cellular uptake and innate immune activation by an immunostimulatory siRNA encapsulated within a liposome carrier in commercially available human peripheral blood mononuclear cells (PBMCs)...
2016: Biological & Pharmaceutical Bulletin
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