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Tumor immune recognition

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https://www.readbyqxmd.com/read/28438506/diacylglycerol-kinase-%C3%AE-limits-cytokine-dependent-expansion-of-cd8-t-cells-with-broad-antitumor-capacity
#1
Elena Andrada, Rosa Liébana, Isabel Merida
Interleukin-2 and -15 drive expansion/differentiation of cytotoxic CD8(+) T cells that eliminate targets via antigen-independent killing. This property is clinically relevant for the improvement of T cell-based antitumor therapies. Diacylglycerol kinase α and ζ (DGKα/ζ) metabolize the diacylglycerol generated following antigen recognition by T lymphocytes. Enhanced expression of these two lipid kinases in tumor-infiltrating CD8(+) T cells promotes a hyporesponsive state that contributes to tumor immune escape...
April 14, 2017: EBioMedicine
https://www.readbyqxmd.com/read/28430646/immunotherapeutic-target-expression-on-breast-tumors-can-be-amplified-by-hormone-receptor-antagonism-a-novel-strategy-for-enhancing-efficacy-of-targeted-immunotherapy
#2
Ritika Jaini, Matthew G Loya, Charis Eng
Immunotherapy has historically been successful in highly antigenic tumors but has shown limited therapeutic efficacy in non-antigenic tumors such as breast cancers. Our previous studies in autoimmunity have demonstrated that increased antigen load within a tissue enhances immune reactivity against it. We therefore hypothesized that enhancing expression of target proteins on breast tumors can increase efficacy of targeted immunotherapy. We hypothesized that antagonism of the estrogen receptor (ER) can increase expression of targets that are hormonally regulated and facilitate enhanced tumor recognition by targeted immunotherapy...
March 1, 2017: Oncotarget
https://www.readbyqxmd.com/read/28426690/phenotypic-characterization-and-anticancer-capacity-of-cd8-cytokine-induced-killer-cells-after-antigen-induced-expansion
#3
Jianhua Liu, Lu Wang, Yaoling Wang, Wenjie Zhang, Yilin Cao
Cytokine-induced killer cells (CIK) have been used in clinic for adoptive immunotherapy in a variety of malignant tumors and have improved the prognosis of cancer patients. However, there are individual differences in the CIK cell preparations including the obvious differences in the ratio of effector CIK cells among different cancer patients. Infusion of such heterogeneous immune cell preparation is an important factor that would affect the therapeutic efficacy. We report here the enrichment and expansion of CD8+ cells from CIK cells cultured for one week using magnetic activated cell sorting (MACS)...
2017: PloS One
https://www.readbyqxmd.com/read/28422714/toll-like-receptor-3-as-an-immunotherapeutic-target-for-kras-mutated-colorectal-cancer
#4
Radhashree Maitra, Titto Augustine, Yitzchak Dayan, Carol Chandy, Matthew Coffey, Sanjay Goel
New therapeutic interventions are essential for improved management of patients with metastatic colorectal cancer (mCRC). This is especially critical for those patients whose tumors harbor a mutation in the KRAS oncogene (40-45% of all patients). This patient cohort is excluded from receiving anti-EGFR monoclonal antibodies that have added a significant therapeutic benefit for KRAS wild type CRC patients. Reovirus, a double stranded (ds) RNA virus is in clinical development for patients with chemotherapy refractory KRAS mutated tumors...
April 4, 2017: Oncotarget
https://www.readbyqxmd.com/read/28421060/the-heme-metabolite-carbon-monoxide-facilitates-kshv-infection-by-inhibiting-tlr4-signaling-in-endothelial-cells
#5
Sara Botto, Jean K Gustin, Ashlee V Moses
Kaposi sarcoma herpesvirus (KSHV) is the etiologic agent of Kaposi sarcoma (KS) and certain rare B cell lymphoproliferative disorders. KSHV infection of endothelial cells (EC) in vitro increases expression of the inducible host-encoded enzyme heme oxygenase-1 (HO-1), which is also strongly expressed in KS tumors. HO-1 catalyzes the rate-limiting step in the conversion of heme into iron, biliverdin and the gasotransmitter carbon monoxide (CO), all of which share anti-apoptotic, anti-inflammatory, pro-survival, and tumorigenic activities...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/28420679/tumor-microenvironment-targeting-and-responsive-peptide-based-nanoformulations-for-improved-tumor-therapy
#6
Hao Qin, Yanping Ding, Ayeesha Mujeeb, Ying Zhao, Guangjun Nie
Tumor microenvironment participates in all stages of tumor progression and has emerged as a promising therapeutic target for cancer therapy. Rapid progress in the field of molecular self-assembly using various biological molecules has resulted in the fabrication of nanoformulations, specifically targeting and regulating the microenvironment components to inhibit tumor malignancies. This inhibition process is based on the differentiating biophysicochemical cues guiding tumor and normal tissue microenvironments...
April 18, 2017: Molecular Pharmacology
https://www.readbyqxmd.com/read/28410529/ifn%C3%AE-enhances-cytotoxic-efficiency-of-the-cytotoxic-t-lymphocytes-against-human-glioma-cells
#7
Shengwen Shao, Eric Risch, Danielle Burner, Lingeng Lu, Boris Minev, Wenxue Ma
Cytotoxic T lymphocytes (CTLs) are a key player in cancer immunotherapies, and MHC class I molecules on the cell surface are crucial for cellular recognition. However, the aberrant expression of MHC class I molecules is frequently found in various malignancies. IFNγ has dual functions in cancer progression, and its effect on tumor immunity is controversial. To investigate whether IFNγ can enhance cytotoxic efficiency of the tumor antigen-specific CTLs, we generated the CTLs using modified human dendritic cells as antigen presenting cells, then studied the activities of CTLs on human leukocyte antigen (HLA)-A2 positive glioma cells treated with, or without IFNγ...
April 11, 2017: International Immunopharmacology
https://www.readbyqxmd.com/read/28410296/neoantigen-discovery-in-human-cancers
#8
Elaine R Mardis
Cancer is caused by alterations to DNA that ultimately are translated into altered proteins with unique amino acid sequences when compared with their counterparts in normal cells. By inference, these altered proteins have the potential to elicit immune responses such as T-cell recognition, if properly presented by the immune system following protein degradation and major histocompatibility complex binding. Historically, identifying tumor-specific mutant antigens was painstaking work that involved molecular cloning and immune screening...
March 2017: Cancer Journal
https://www.readbyqxmd.com/read/28377481/characterization-of-an-immunogenic-mutation-in-a-patient-with-metastatic-triple-negative-breast-cancer
#9
Yasmine Assadipour, Nikolaos Zacharakis, Jessica S Crystal, Todd D Prickett, Jared J Gartner, Robert P T Somerville, Hui Xu, Mary A Black, Li Jia, Harshini Chinnasamy, Isaac Kriley, Lily Lu, John R Wunderlich, Zhili Zheng, Yong-Chen Lu, Paul F Robbins, Steven A Rosenberg, Stephanie L Goff, Steven A Feldman
The administration of autologous tumor infiltrating lymphocytes (TIL) can mediate durable tumor regressions in patients with melanoma likely based on the recognition of immunogenic somatic mutations expressed by the cancer. There is limited data regarding the immunogenicity of mutations in breast cancer. We sought to identify immunogenic non-synonymous mutations in a patient with triple-negative breast cancer (TNBC) in order to identify and isolate mutation-reactive TIL for possible use in adoptive cell transfer...
April 4, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28373361/pancreatic-cancer-a-riddle-wrapped-in-a-mystery-inside-an-enigma
#10
EDITORIAL
Erkut Borazanci, Chi V Dang, Robert W Robey, Susan E Bates, John A Chabot, Daniel D Von Hoff
Pancreatic ductal adenocarcinoma (PDAC) is one of the most difficult-to-treat cancers. With an increasing incidence and inability to make major progress, it represents the very definition of unmet medical need. Progress has been made in understanding the basic biology-systematic genomic sequencing has led to the recognition that PDAC is not typically a heavily mutated tumor, although there are exceptions. The most consistently mutated genes are KRAS, CDKN2A, TP53, and SMAD4/DPC4 Study of familial PDAC has led to the recognition that a variety of defects in DNA repair genes can be associated with the emergence of pancreatic cancer...
April 1, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28372998/differential-induction-of-immunogenic-cell-death-and-interferon-expression-in-cancer-cells-by-structured-ssrnas
#11
Jaewoo Lee, Youngju Lee, Li Xu, Rebekah White, Bruce A Sullenger
Activation of the RNA-sensing pattern recognition receptor (PRR) in cancer cells leads to cell death and cytokine expression. This cancer cell death releases tumor antigens and damage-associated molecular patterns (DAMPs) that induce anti-tumor immunity. However, these cytokines and DAMPs also cause adverse inflammatory and thrombotic complications that can limit the overall therapeutic benefits of PRR-targeting anti-cancer therapies. To overcome this problem, we generated and evaluated two novel and distinct ssRNA molecules (immunogenic cell-killing RNA [ICR]2 and ICR4)...
March 31, 2017: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://www.readbyqxmd.com/read/28348977/taming-tumor-glycolysis-and-potential-implications-for-immunotherapy
#12
REVIEW
Shanmugasundaram Ganapathy-Kanniappan
Immune evasion and deregulation of energy metabolism play a pivotal role in cancer progression. Besides the coincidence in their historical documentation and concurrent recognition as hallmarks of cancer, both immune evasion and metabolic deregulation may be functionally linked as well. For example, the metabolic phenotype, particularly tumor glycolysis (aerobic glycolysis), impacts the tumor microenvironment (TME), which in turn acts as a major barrier for successful targeting of cancer by antitumor immune cells and other therapeutics...
2017: Frontiers in Oncology
https://www.readbyqxmd.com/read/28347245/cancer-stem-cells-the-potential-role-of-autophagy-proteolysis-and-cathepsins-in-glioblastoma-stem-cells
#13
REVIEW
Joachim Bischof, Mike-Andrew Westhoff, Johanna Elisabeth Wagner, Marc-Eric Halatsch, Stephanie Trentmann, Uwe Knippschild, Christian Rainer Wirtz, Timo Burster
One major obstacle in cancer therapy is chemoresistance leading to tumor recurrence and metastasis. Cancer stem cells, in particular glioblastoma stem cells, are highly resistant to chemotherapy, radiation, and immune recognition. In case of immune recognition, several survival mechanisms including, regulation of autophagy, proteases, and cell surface major histocompatibility complex class I molecules, are found in glioblastoma stem cells. In different pathways, cathepsins play a crucial role in processing functional proteins that are necessary for several processes and proper cell function...
March 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28343731/endoplasmic-reticulum-aminopeptidase-2-a-common-immunological-link-to-adverse-pregnancy-outcomes-and-cancer-clearance
#14
Eun D Lee
Endoplasmic Reticulum Aminopeptidase 2 (ERAP2) trims HLA class I-binding peptides, determining the peptide repertoire presented for immune recognition. Variation in the ERAP2 amino acid sequence could affect the ability of some fetuses and tumors to achieve immune evasion. For example, homozygosity for an ERAP2 variant that has increased trimming efficiency for hydrophobic molecules has never been detected in mothers and fetuses. Thus, it is possible that this single nucleotide polymorphism (SNP) in the ERAP2 gene has been selected against in order to prevent alteration of the immune privileged uterine environment, and to allow tumors to escape immune recognition...
March 18, 2017: Placenta
https://www.readbyqxmd.com/read/28337274/decitabine-treatment-sensitizes-tumor-cells-to-t-cell-mediated-cytotoxicity-in-patients-with-myelodysplastic-syndromes
#15
Zheng Zhang, Qi He, Ying Tao, Juan Guo, Feng Xu, Ling-Yun Wu, You-Shan Zhao, Dong Wu, Li-Yu Zhou, Ji-Ying Su, Lu-Xi Song, Chao Xiao, Xiao Li, Chun-Kang Chang
Decitabine treatment improves immunological recognition that increases expression of cancer-testis antigens (CTAs) against solid tumors. The mechanisms of decitabine enhancement of immunogenicity when used for patients with myelodysplastic syndromes (MDS) remain unclear. In the present study, we found relatively low baseline expression of MAGE-A1, MAGE-A3, and SP17 in MDS-derived cell lines. Decitabine treatment significantly improved MAGE-A1, MAGE-A3, and SP17 expression in these cell lines and in MDS patients...
2017: American Journal of Translational Research
https://www.readbyqxmd.com/read/28336489/current-applications-selection-and-possible-mechanisms-of-actions-of-synbiotics-in-improving-the-growth-and-health-status-in-aquaculture-a-review
#16
REVIEW
Truong-Giang Huynh, Ya-Li Shiu, Thanh-Phuong Nguyen, Quoc-Phu Truong, Jiann-Chu Chen, Chun-Hung Liu
Synbiotics, a conjunction between prebiotics and probiotics, have been used in aquaculture for over 10 years. However, the mechanisms of how synbiotics work as growth and immunity promoters are far from being unraveled. Here, we show that a prebiotic as part of a synbiotic is hydrolyzed to mono- or disaccharides as the sole carbon source with diverse mechanisms, thereby increasing biomass and colonization that is established by specific crosstalk between probiotic bacteria and the surface of intestinal epithelial cells of the host...
May 2017: Fish & Shellfish Immunology
https://www.readbyqxmd.com/read/28323141/mechanistic-and-pharmacologic-insights-on-immune-checkpoint-inhibitors
#17
REVIEW
Randy F Sweis, Jason J Luke
The concept of augmenting the immune system to eradicate cancer dates back at least a century. A major resurgence in cancer immunotherapy has occurred over the past decade since the identification and targeting of negative regulators with antibody therapies to augment the anti-tumor immune response. Unprecedented responses across a broad array of cancer types elevated this class of therapies to the forefront of cancer treatment. The most successful drugs to date target the cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) and programmed cell death-1 (PD-1) pathways...
March 18, 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/28322156/recent-findings-on-the-application-of-toll-like-receptors-agonists-in-cancer-therapy
#18
Martina Mikulandra, Jasminka Pavelic, Tanja Matijevic Glavan
The immune system's first line of defense is innate immunity, largely based on a large family of pattern recognition receptors (PRRs) that recognize evolutionary conserved molecular motifs on pathogens called pathogen-associated molecular patterns (PAMPs). The most extensively studied family of PRRs are Toll-like receptors (TLRs), which can trigger various cellular pathways after ligand stimulation. Their role in cancer is still unresolved as there are many different studies showing contradictory results. TLRs have been associated with both tumor progression and immunosuppression as well as with apoptosis and immune system activation...
March 20, 2017: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/28300171/quantum-dot-based-suspension-microarray-for-multiplex-detection-of-lung-cancer-markers-preclinical-validation-and-comparison-with-the-luminex-xmap-%C3%A2-system
#19
Regina Bilan, Amagoia Ametzazurra, Kristina Brazhnik, Sergio Escorza, David Fernández, María Uríbarri, Igor Nabiev, Alyona Sukhanova
A novel suspension multiplex immunoassay for the simultaneous specific detection of lung cancer markers in bronchoalveolar lavage fluid (BALF) clinical samples based on fluorescent microspheres having different size and spectrally encoded with quantum dots (QDEM) was developed. The designed suspension immunoassay was validated for the quantitative detection of three lung cancer markers in BALF samples from 42 lung cancer patients and 10 control subjects. Tumor markers were detected through simultaneous formation of specific immune complexes consisting of a capture molecule, the target antigen, and biotinylated recognition molecule on the surface of the different QDEM in a mixture...
March 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28287848/immunomodulating-and-immunoresistance-properties-of-cancer-initiating-cells-implications-for-the-clinical-success-of-immunotherapy
#20
REVIEW
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...
April 2017: Immunological Investigations
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