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Tumor immune recognition

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https://www.readbyqxmd.com/read/29054272/insights-on-the-hla-binding-peptidome-in-cancer
#1
Douglas F Lake
The intracellular compartments for proteolytic antigen processing in tumor cells produce peptides that are presented by MHC molecules to T cells. But first, the ubiquitin ligase system tags defective, misfolded, aged, and unstable proteins for degradation through the proteasome. Ubiqitinated proteins are unfolded and fed into the barrel-shaped core of the proteasome where a collection of multiple different proteases cleave proteins into oligopeptides. After exiting the proteasome, these oligopeptides are either completely degraded into amino acids or trimmed at the N- and C-termini so that they bind to transporter associated with antigen processing (TAP)...
2017: Enzymes
https://www.readbyqxmd.com/read/29054270/the-peptidome-comes-of-age-mass-spectrometry-based-characterization-of-the-circulating-cancer-peptidome
#2
David W Greening, Eugene A Kapp, Richard J Simpson
Peptides play a seminal role in most physiological processes acting as neurotransmitters, hormones, antibiotics, and immune regulation. In the context of tumor biology, it is hypothesized that endogenous peptides, hormones, cytokines, growth factors, and aberrant degradation of select protein networks (e.g., enzymatic activities, protein shedding, and extracellular matrix remodeling) are fundamental in mediating cancer progression. Analysis of peptides in biological fluids by mass spectrometry holds promise of providing sensitive and specific diagnostic and prognostic information for cancer and other diseases...
2017: Enzymes
https://www.readbyqxmd.com/read/29051161/prostate-cancer-cells-express-more-androgen-receptor-ar-following-androgen-deprivation-improving-recognition-by-ar-specific-t-cells
#3
Brian M Olson, Melissa Gamat, Joseph Seliski, Thomas Sawicki, Justin Jeffery, Leigh Ellis, Charles G Drake, Jamey Weichert, Douglas G McNeel
Androgen deprivation is the primary therapy for recurrent prostate cancer, and agents targeting the androgen receptor (AR) pathway continue to be developed. Because androgen-deprivation therapy (ADT) has immmunostimulatory effects as well as direct antitumor effects, AR-targeted therapies have been combined with other anti-cancer therapies, including immunotherapies. Here, we sought to study whether an antigen-specific mechanism of resistance to ADT (overexpression of the AR) may result in enhanced AR-specific T-cell immune recognition, and whether this might be strategically combined with an antitumor vaccine targeting the AR...
October 19, 2017: Cancer Immunology Research
https://www.readbyqxmd.com/read/29050360/immunomodulatory-and-antitumor-effects-of-type-i-interferons-and-their-application-in-cancer-therapy
#4
REVIEW
Ruan F V Medrano, Aline Hunger, Samir Andrade Mendonça, José Alexandre M Barbuto, Bryan E Strauss
During the last decades, the pleiotropic antitumor functions exerted by type I interferons (IFNs) have become universally acknowledged, especially their role in mediating interactions between the tumor and the immune system. Indeed, type I IFNs are now appreciated as a critical component of dendritic cell (DC) driven T cell responses to cancer. Here we focus on IFN-α and IFN-β, and their antitumor effects, impact on immune responses and their use as therapeutic agents. IFN-α/β share many properties, including activation of the JAK-STAT signaling pathway and induction of a variety of cellular phenotypes...
September 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/29042925/calreticulin-is-an-effective-immunologic-adjuvant-to-tumor-associated-antigens
#5
Jun Wang, Zhi Peng Gao, Song Qin, Chang Bai Liu, Li Li Zou
As a key molecule involved in cell recognition, calreticulin (CRT) may be expressed on the surface of (pre-) apoptotic cells and provide the signal that is recognized by dendritic cells (DCs) or other antigen presenting cells (APCs), which results in phagocytosis. Within the APCs, tumor-associated antigens (TAAs) may be subsequently presented to T lymphocytes, which triggers a specific antitumor immune response. It has been hypothesized that CRT is able to act as the immunologic adjuvant and translocate itself and TAAs to the cell surface and induce a specific antitumor immune response...
October 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/29029468/resveratrol-promotes-mica-b-expression-and-natural-killer-cell-lysis-of-breast-cancer-cells-by-suppressing-c-myc-mir-17-pathway
#6
Jie Pan, Jiaying Shen, Wengong Si, Chengyong Du, Danni Chen, Liang Xu, Minya Yao, Peifen Fu, Weimin Fan
Major histocompatibility complex class I chain-related proteins A and B (MICA and MICB) are important ligands for recognition of tumor cells by immune effector cells. Here, we report that resveratrol upregulated the protein and mRNA expression of MICA and MICB in breast cancer cells, which in turn promoted breast cancer cell lysis by natural killer (NK) cells in vitro and in vivo. Antibodies against NK group 2 member D blocked this effect. The 3'-untranslated regions of MICA and MICB were found to be direct binding targets of miR-17...
September 12, 2017: Oncotarget
https://www.readbyqxmd.com/read/29028369/toll-like-receptors-significance-ligands-signaling-pathways-and-functions-in-mammals
#7
Mallenahally Kusha Vidya, V Girish Kumar, Veerasamy Sejian, Madiajagan Bagath, Govindan Krishnan, Raghavendra Bhatta
This review attempts to cover the implication of the toll-like receptors (TLRs) in controlling immune functions with emphasis on their significance, function, regulation and expression patterns. The tripartite TLRs are type I integral transmembrane receptors that are involved in recognition and conveying of pathogens to the immune system. These paralogs are located on cell surfaces or within endosomes. The TLRs are found to be functionally involved in the recognition of self and non-self-antigens, maturation of DCs and initiation of antigen-specific adaptive immune responses as they bridge the innate and adaptive immunity...
October 13, 2017: International Reviews of Immunology
https://www.readbyqxmd.com/read/29027232/immune-recognition-of-irradiated-cancer-cells
#8
REVIEW
Erik Wennerberg, Claire Vanpouille-Box, Sophia Bornstein, Takahiro Yamazaki, Sandra Demaria, Lorenzo Galluzzi
Ionizing irradiation has been extensively employed for the clinical management of solid tumors, with therapeutic or palliative intents, for decades. Until recently, radiation therapy (RT) was believed to mediate antineoplastic activity mostly (if not only) as a consequence of cancer cell-intrinsic effects. Indeed, the macromolecular damage imposed to malignant cells by RT initiates one or multiple signal transduction cascades that drive a permanent proliferative arrest (cellular senescence) or regulated cell death...
November 2017: Immunological Reviews
https://www.readbyqxmd.com/read/29027231/the-renaissance-of-anti-neoplastic-immunity-from-tumor-cell-demise
#9
REVIEW
Yuting Ma, Jonathan M Pitt, Qingqing Li, Heng Yang
Cancer therapies can temporarily reduce tumor burdens by inducing malignant cell death. However, cancer cure is still far from realization because tumors often gain resistance to current treatment and eventually relapse. Accumulating evidence suggests that successful cancer interventions require anti-tumor immunity. Therapy-induced cell stress responses ultimately result in one or more cell death modalities, including apoptosis, autophagy, necroptosis, and pyroptosis. These irreversible dying processes are accompanied by active or passive release of cell death-associated molecular patterns (CDAMPs), which can be sensed by corresponding pattern recognition receptors (PRR) on tumor-infiltrating immune cells...
November 2017: Immunological Reviews
https://www.readbyqxmd.com/read/29027230/immunogenic-stress-and-death-of-cancer-cells-contribution-of-antigenicity-vs-adjuvanticity-to-immunosurveillance
#10
REVIEW
Norma Bloy, Pauline Garcia, Céline M Laumont, Jonathan M Pitt, Antonella Sistigu, Gautier Stoll, Takahiro Yamazaki, Eric Bonneil, Aitziber Buqué, Juliette Humeau, Jan W Drijfhout, Guillaume Meurice, Steffen Walter, Jens Fritsche, Toni Weinschenk, Hans-Georg Rammensee, Cornelis Melief, Pierre Thibault, Claude Perreault, Jonathan Pol, Laurence Zitvogel, Laura Senovilla, Guido Kroemer
Cancer cells are subjected to constant selection by the immune system, meaning that tumors that become clinically manifest have managed to subvert or hide from immunosurveillance. Immune control can be facilitated by induction of autophagy, as well as by polyploidization of cancer cells. While autophagy causes the release of ATP, a chemotactic signal for myeloid cells, polyploidization can trigger endoplasmic reticulum stress with consequent exposure of the "eat-me" signal calreticulin on the cell surface, thereby facilitating the transfer of tumor antigens into dendritic cells...
November 2017: Immunological Reviews
https://www.readbyqxmd.com/read/29027226/efferocytosis-of-dying-cells-differentially-modulate-immunological-outcomes-in-tumor-microenvironment
#11
REVIEW
Sushil Kumar, David Calianese, Raymond B Birge
Programmed cell death (apoptosis) is an integral part of tissue homeostasis in complex organisms, allowing for tissue turnover, repair, and renewal while simultaneously inhibiting the release of self antigens and danger signals from apoptotic cell-derived constituents that can result in immune activation, inflammation, and autoimmunity. Unlike cells in culture, the physiological fate of cells that die by apoptosis in vivo is their rapid recognition and engulfment by phagocytic cells (a process called efferocytosis)...
November 2017: Immunological Reviews
https://www.readbyqxmd.com/read/29027225/necroptotic-cell-death-in-anti-cancer-therapy
#12
REVIEW
Olga Krysko, Tania Løve Aaes, Valerian E Kagan, Katharina D'Herde, Claus Bachert, Luc Leybaert, Peter Vandenabeele, Dmitri V Krysko
Necroptosis is one the best-characterized forms of regulated necrosis. Necroptosis is mediated by the kinase activities of receptor interacting protein kinase-1 and receptor interacting protein kinase-3, which eventually lead to the activation of mixed lineage kinase domain-like. Necroptosis is characterized by rapid permeabilization of the plasma membrane, which is associated with the release of the cell content and subsequent exposure of damage-associated molecular patterns (DAMPs) and cytokines/chemokines...
November 2017: Immunological Reviews
https://www.readbyqxmd.com/read/29018797/micrornas-make-the-call-in-cancer-personalized-medicine
#13
REVIEW
Simone Detassis, Margherita Grasso, Valerio Del Vescovo, Michela A Denti
Since their discovery and the advent of RNA interference, microRNAs have drawn enormous attention because of their ubiquitous involvement in cellular pathways from life to death, from metabolism to communication. It is also widely accepted that they possess an undeniable role in cancer both as tumor suppressors and tumor promoters modulating cell proliferation and migration, epithelial-mesenchymal transition and tumor cell invasion and metastasis. Moreover, microRNAs can even affect the tumor surrounding environment influencing angiogenesis and immune system activation and recruitment...
2017: Frontiers in Cell and Developmental Biology
https://www.readbyqxmd.com/read/28993779/natural-killer-cell-response-to-chemotherapy-stressed-cancer-cells-role-in-tumor-immunosurveillance
#14
REVIEW
Alessandra Zingoni, Cinzia Fionda, Cristiana Borrelli, Marco Cippitelli, Angela Santoni, Alessandra Soriani
Natural killer (NK) cells are innate cytotoxic lymphoid cells that actively prevent neoplastic development, growth, and metastatic dissemination in a process called cancer immunosurveillance. An equilibrium between immune control and tumor growth is maintained as long as cancer cells evade immunosurveillance. Therapies designed to kill cancer cells and to simultaneously sustain host antitumor immunity are an appealing strategy to control tumor growth. Several chemotherapeutic agents, depending on which drugs and doses are used, give rise to DNA damage and cancer cell death by means of apoptosis, immunogenic cell death, or other forms of non-apoptotic death (i...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28990073/nod-receptor-and-tlr9-modulation-in-severe-acute-pancreatitis%C3%A2-induced-intestinal-injury
#15
Yupeng Yan, Bin Lu, Pengyang Li, Ji Wang
Severe acute pancreatitis (SAP) has a rapid onset and may cause multiple organ dysfunction syndrome (MODS), which has high mortality. Nucleotide binding oligomerization domain (NOD) receptor and Toll‑like receptor 9 (TLR9), a pattern recognition receptor in innate immunity, are involved in inflammation, immunity and pathogen recognition. The role and mechanism of the NOD receptor and TLR9 in early MODS of SAP‑induced intestinal injury, however, remain unclear. Wistar rats were divided into control, SAP, TLR9 inhibitor and NOD receptor activation groups...
September 29, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28977839/genetic-defects-of-the-irf1-mediated-major-histocompatibility-complex-class-i-antigen-presentation-pathway-occur-prevalently-in-the-jak2-gene-in-non-small-cell-lung-cancer
#16
Tao Shen, Zhengming Chen, Zhizhuang Joe Zhao, Jie Wu
Recognition of major histocompatibility complex (MHC) class I antigens on tumor cells by cytotoxic T cells is involved in T cell-mediated tumor immune surveillance and immune checkpoint therapy. The interferon-γ (IFNγ)-IRF1 signaling pathway regulates MHC class I antigen presentation. To examine genetic defects of the IFNγ-IRF1 pathway in non-small cell lung cancer (NSCLC), we analyzed The Cancer Genome Atlas (TCGA) lung adenocarcinoma (LuAd) and lung squamous cell carcinoma (LuSc) data. Loss-of-function (LOF) genetic alterations of the IFNγ-IRF1 pathway genes (IFNGR1, IFNGR2, JAK1, JAK2, STAT1, IRF1) were found in 64 (6...
September 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28976209/avelumab-and-other-recent-advances-in-merkel-cell-carcinoma
#17
Praveen K Bommareddy, Howard L Kaufman
Merkel-cell carcinoma (MCC) is a rare but aggressive form of skin cancer that occurs in the elderly, is associated with UV radiation and immunosuppression. Initial treatment consists of wide excision with adjuvant radiation. Although the tumor is sensitive to chemotherapy, long-term survival is unusual and there had been no US FDA-approved drugs prior to 2017. The recognition that MCC is associated with the Merkel cell polyomavirus occurs more commonly in immune-compromised patients and tumors express PD-L1 suggested testing immunotherapy...
October 4, 2017: Future Oncology
https://www.readbyqxmd.com/read/28959257/the-potential-and-challenges-of-exploiting-the-vast-but-dynamic-neoepitope-landscape-for-immunotherapy
#18
Els M E Verdegaal, Sjoerd H van der Burg
Somatic non-synonymous mutations in the DNA of tumor cells may result in the presentation of tumor-specific peptides to T cells. The recognition of these so-called neoepitopes now has been firmly linked to the clinical success of checkpoint blockade and adoptive T cell therapy. Following proof-of-principle studies in preclinical models there was a surge of strategies to identify and exploit genetically defined clonally expressed neoepitopes. These approaches assume that neoepitope availability remains stable during tumor progression but tumor genetics has taught us otherwise...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28959256/functionally-active-fc-mutant-antibodies-recognizing-cancer-antigens-generated-rapidly-at-high-yields
#19
Kristina M Ilieva, Judit Fazekas-Singer, Daniela Y Achkova, Tihomir S Dodev, Silvia Mele, Silvia Crescioli, Heather J Bax, Anthony Cheung, Panagiotis Karagiannis, Isabel Correa, Mariangela Figini, Rebecca Marlow, Debra H Josephs, Andrew J Beavil, John Maher, James F Spicer, Erika Jensen-Jarolim, Andrew N Tutt, Sophia N Karagiannis
Monoclonal antibodies find broad application as therapy for various types of cancer by employing multiple mechanisms of action against tumors. Manipulating the Fc-mediated functions of antibodies that engage immune effector cells, such as NK cells, represents a strategy to influence effector cell activation and to enhance antibody potency and potentially efficacy. We developed a novel approach to generate and ascertain the functional attributes of Fc mutant monoclonal antibodies. This entailed coupling single expression vector (pVitro1) antibody cloning, using polymerase incomplete primer extension (PIPE) polymerase chain reaction, together with simultaneous Fc region point mutagenesis and high yield transient expression in human mammalian cells...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28944078/a-pore-forming-protein-implements-vlr-activated-complement-cytotoxicity-in-lamprey
#20
Fenfang Wu, Bo Feng, Yong Ren, Di Wu, Yue Chen, Shengfeng Huang, Shangwu Chen, Anlong Xu
Lamprey is a basal vertebrate with a unique adaptive immune system, which uses variable lymphocyte receptors (VLRs) for antigen recognition. Our previous study has shown that lamprey possessed a distinctive complement pathway activated by VLR. In this study, we identified a natterin family member-lamprey pore-forming protein (LPFP) with a jacalin-like lectin domain and an aerolysin-like pore-forming domain. LPFP had a high affinity with mannan and could form oligomer in the presence of mannan. LPFP could deposit on the surface of target cells, form pore-like complex resembling a wheel with hub and spokes, and mediate powerful cytotoxicity on target cells...
2017: Cell Discovery
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