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Anti-tumor T cell response

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https://www.readbyqxmd.com/read/28454423/the-nutritional-herb-epimedium-grandiflorum-inhibits-the-growth-in-a-model-for-the-luminal-a-molecular-subtype-of-breast-cancer
#1
Nitin T Telang, Gou Li, Meena Katdare, Daniel W Sepkovic, H Leon Bradlow, George Y C Wong
The Luminal A subtype of breast cancer expresses the estrogen receptor (ER)-α and progesterone receptor (PR), but not the human epidermal growth factor receptor (HER)-2 oncogene. This subtype of breast cancer responds to endocrine therapy involving the use of selective estrogen receptor modulators and/or inhibitors of estrogen biosynthesis. However, these therapeutic agents are frequently associated with long-term systemic toxicity and acquired tumor resistance, emphasizing the need to identify non-toxic alternative treatments for chemo-endocrine therapy responsive breast cancer...
April 2017: Oncology Letters
https://www.readbyqxmd.com/read/28454381/optimized-construction-of-muc1-vntrn-dna-vaccine-and-its-anti-pancreatic-cancer-efficacy
#2
Yuan-Feng Gong, Quan-Bo Zhou, Ya-Di Liao, Cong Mai, Tie-Jun Chen, Yun-Qiang Tang, Ru-Fu Chen
Considering mucin 1-variable number tandem repeat (MUC1-VNTRn) as a novel target for pancreatic cancer immunotherapy, the present study aimed to screen and identify the pVAX1-MUC1-VNTRn DNA vaccine with the strongest immunogenicity. Following construction of a pVAX1-MUC1-VNTRn plasmid, immature dendritic cells (DCs) were subjected to transfection, and mature DCs were then co-cultured with autologous T-cells. The numbers of cytotoxic T lymphocytes (CTLs) secreting interferon (IFN)-γ were determined using an enzyme-linked immunospot assay, and CytoTox(®) was also used to examine the MUC1-VNTRn-specific Lethal effect of CTLs on Capan2 cells...
April 2017: Oncology Letters
https://www.readbyqxmd.com/read/28453931/ugi-reaction-derived-%C3%AE-acyl-aminocarboxamides-bind-to-phosphatidylinositol-3-kinase-related-kinases-inhibit-hsf1-dependent-heat-shock-response-and-induce-apoptosis-in-multiple-myeloma-cells
#3
Matthias Bach, Anna Lehmann, Daniela Brünnert, Jens T Vanselow, Andreas Hartung, Ralf C Bargou, Ulrike Holzgrabe, Andreas Schlosser, Manik Chatterjee
The heat shock transcription factor 1 (HSF1) has been identified as a therapeutic target for pharmacological treatment of multiple myeloma (MM) However, direct therapeutic targeting of HSF1 function seems to be difficult due to the shortage of clinically suitable pharmacological inhibitors. We utilized the Ugi multicomponent reaction to create a small, but smart library of α-acyl aminocarboxamides, and evaluated their ability to suppress heat shock response (HSR) in MM cells. Using the INA-6 cell line as MM model, and the strictly HSF1 dependent HSP72 induction as a HSR model, we identified potential HSF1 inhibitors...
April 28, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28449473/anti-pd-1-pd-l1-antibody-versus-conventional-chemotherapy-for-previously-treated-advanced-non-small-cell-lung-cancer-a-meta-analysis-of-randomized-controlled-trials
#4
Yongxun Zhuansun, Fengting Huang, Yumo Du, Lin Lin, Rui Chen, Jianguo Li
BACKGROUND: The anti-PD-1/PD-L1 monoclonal antibody has showed promising results in various cancers via enhancing T cell functions. However, many questions remain in the role and safety in previously-treated, advanced non-small-cell lung cancer (NSCLC). Thus, we conducted a meta-analysis incorporating all available evidences to evaluate the efficacy and safety of anti-PD-1/PD-L1 antibody compared with chemotherapy. METHODS: PubMed, Web of Science and the Cochrane Library database were searched for the studies about the efficacy and safety of anti-PD-1/PD-L1 antibody in previously-treated, progressive NSCLC patients...
March 2017: Journal of Thoracic Disease
https://www.readbyqxmd.com/read/28448494/integrin-%C3%AE-1-activation-induces-an-anti-melanoma-host-response
#5
Laila Ritsma, Ipsita Dey-Guha, Nilesh Talele, Xavier Sole, Salony, Joeeta Chowdhury, Kenneth N Ross, Sridhar Ramaswamy
TGF-β is a cytokine thought to function as a tumor promoter in advanced malignancies. In this setting, TGF-β increases cancer cell proliferation, survival, and migration, and orchestrates complex, pro-tumorigenic changes in the tumor microenvironment. Here, we find that in melanoma, integrin β1-mediated TGF-β activation may also produce tumor suppression via an altered host response. In the A375 human melanoma cell nu/nu xenograft model, we demonstrate that cell surface integrin β1-activation increases TGF-β activity, resulting in stromal activation, neo-angiogenesis and, unexpectedly for this nude mouse model, increase in the number of intra-tumoral CD8+ T lymphocytes within the tumor microenvironment...
2017: PloS One
https://www.readbyqxmd.com/read/28445973/plasmodium-parasite-as-an-effective-hepatocellular-carcinoma-antigen-glypican-3-delivery-vector
#6
Quan Liu, Yijun Yang, Xuefang Tan, Zhu Tao, Dickson Adah, Songlin Yu, Junnan Lu, Siting Zhao, Limei Qin, Li Qin, Xiaoping Chen
We have previously demonstrated that malaria parasite infection has an anti-tumor effect in a mouse model. This research aimed to investigate the possibility of using Plasmodium parasite as a novel vaccine vector for hepatocellular carcinoma (HCC) immunotherapy. We constructed a Plasmodium yoelii 17XNL strain (P.y) expressing murine glypican-3 (GPC3) protein (P.y-GPC3), and examined its therapeutic potency in a murine Hepa1-6-induced hepatoma model that highly expressed GPC3 protein. The prerequisites for invoking a CD8+ T cell response were assessed after P...
April 11, 2017: Oncotarget
https://www.readbyqxmd.com/read/28445856/procyanidin-a-kind-of-biological-flavonoid-induces-protective-anti-tumor-immunity-and-protects-mice-from-lethal-b16f10-challenge
#7
Lina Zhang, Shuang Wang, Zeyuan Liu, Li Zhang, Shanzheng Wang, Bin Wang
Recently, increasing evidences show that procyanidin (PC) modulate immune responses in human. To evaluate adjuvant effects of PC on vaccine immune modulation and anti-tumor activity, we formulated PC with B16F10 tumor antigen as tumor vaccine to immune C57BL/6 mice and used intramuscular injection before challenge with tumor B16F10 cells. Our results revealed that PC enhanced T cell-mediated immune responses both in vitro and in vivo. Moreover, the B16F10 tumor vaccine induced some degree of anti-tumor effects as evaluated by the inhibition of tumor growth and the prolongation of survival...
April 23, 2017: International Immunopharmacology
https://www.readbyqxmd.com/read/28444111/pattern-recognition-receptors-immune-targets-to-enhance-cancer-immunotherapy
#8
T Shekarian, S Valsesia-Wittmann, J Brody, M C Michallet, S Depil, C Caux, A Marabelle
Durable tumor responses and significant levels of disease control rates have been described in more than 20 advanced/metastatic cancer types with B7-family immune checkpoint-targeted anti-CTLA-4, anti-PD-1, and anti-PD-L1 monoclonal antibodies. These results and the recent approvals of ipilimumab, pembrolizumab, nivolumab and atezolizumab are currently revolutionizing the way we envision the future of cancer care. However these clinical benefits are not observed in all cancer types and in every patient. Therefore, our clinical challenge is to identify therapeutic strategies which could overcome the primary and secondary resistances to these novel cancer immunotherapies...
April 21, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/28443470/a-multi-target-protein-of-htertr-fam96a-presents-significant-anticancer-potent-in-the-treatment-of-hepatocellular-carcinoma
#9
Meng-Yu Zhang, Jie-Ping Wang
The abilities to escape apoptosis induced by anticancer drugs are an essential factor of carcinogenesis and a hallmark of resistance to cancer therapy. In this study, we identified hTERTR-FAM96A (human telomerase reverse transcriptase-family with sequence similarity 96 member A) as a new efficient agent for apoptosome-activating and anti-tumor protein and investigated the potential tumor suppressor function in hepatocellular carcinoma. The hTERTR-FAM96A fusion protein was constructed by genetic engineering and its anticancer function of hTERTR-FAM96A was explored in vitro and in vivo by investigating the possible preclinical outcomes...
April 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28442214/regulatory-t-cells-as-suppressors-of-anti-tumor-immunity-role-of-metabolism
#10
REVIEW
Veronica De Rosa, Francesca Di Rella, Antonio Di Giacomo, Giuseppe Matarese
Novel concepts in immunometabolism support the hypothesis that glucose consumption is also used to modulate anti-tumor immune responses, favoring growth and expansion of specific cellular subsets defined in the past as suppressor T cells and currently reborn as regulatory T (Treg) cells. During the 1920s, Otto Warburg and colleagues observed that tumors consumed high amounts of glucose compared to normal tissues, even in the presence of oxygen and completely functioning mitochondria. However, the role of the Warburg Effect is still not completely understood, particularly in the context of an ongoing anti-tumor immune response...
April 11, 2017: Cytokine & Growth Factor Reviews
https://www.readbyqxmd.com/read/28440447/anti%C3%A2-inflammatory-effects-of-oxymatrine-on-rheumatoid-arthritis-in-rats-via-regulating-the-imbalance-between-treg-and-th17-cells
#11
Ailing Ma, Yongya Yang, Qiuyang Wang, Yin Wang, Jing Wen, Yanli Zhang
Oxymatrine (OMT), a monosomic alkaloid extracted from the Chinese herb, Sophora flavescens Ait, has long been used as a traditional Chinese medicine for the treatment of inflammatory diseases. The aim of the present study was to investigate the potential anti‑inflammatory effect of OMT, and its modulation on imbalance between regulatory T (Treg) cells and T helper (Th) 17 cells in rats with collagen‑induced arthritis (CIA). Sprague‑Dawley rats were immunized with type II collagen and following a second collagen immunization, the rats were treated with OMT or dexamethasone (DXM) intraperitoneally once a day for 43 days...
April 19, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28438552/immunomodulation-of-autoimmune-arthritis-by-pro-inflammatory-cytokines
#12
REVIEW
Eugene Y Kim, Kamal D Moudgil
Pro-inflammatory cytokines promote autoimmune inflammation and tissue damage, while anti-inflammatory cytokines help resolve inflammation and facilitate tissue repair. Over the past few decades, this general feature of cytokine-mediated events has offered a broad framework to comprehend the pathogenesis of autoimmune and other immune-mediated diseases, and to successfully develop therapeutic approaches for diseases such as rheumatoid arthritis (RA). Anti-tumor necrosis factor-α (TNF-α) therapy is a testimony in support of this endeavor...
April 21, 2017: Cytokine
https://www.readbyqxmd.com/read/28438506/diacylglycerol-kinase-%C3%AE-limits-cytokine-dependent-expansion-of-cd8-t-cells-with-broad-antitumor-capacity
#13
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/28431920/the-microbiome-in-anti-cancer-therapy
#14
REVIEW
Stavros Bashiardes, Timur Tuganbaev, Sara Federici, Eran Elinav
The commensal microbiome constitutes an important modulator of host physiology and risk of disease, including cancer development and progression. Lately, the microbiome has been suggested to modulate the efficacy of anti-cancer treatment. Examples include chemotherapy and total body irradiation-induced barrier function disruption, leading to microbial efflux that drives activation of anti-tumorigenic T cells; Microbiome-driven release of reactive oxygen species contributing to the efficacy of platinum salts; and microbiome-induced immune priming promoting the anti-tumor effects of alkylating chemotherapy and immune checkpoint inhibitors...
April 18, 2017: Seminars in Immunology
https://www.readbyqxmd.com/read/28429765/repolarizing-macrophages-improves-breast-cancer-therapy
#15
Luca Cassetta, Jeffrey W Pollard
Tumor-associated macrophages (TAMs) contribute to breast cancer progression and dissemination; TAM-targeting strategies aimed at their reprogramming show promising preclinical results. In a new report Guerriero and colleagues demonstrate that a novel HDAC Class IIa inhibitor, TMP195, can reprogram monocytes and macrophages in the tumor into cells able to sustain a robust CD8 T cell-mediated anti-tumoral immune response.
April 21, 2017: Cell Research
https://www.readbyqxmd.com/read/28425751/development-of-red-blood-cell-autoantibodies-following-treatment-with-checkpoint-inhibitors-a-new-class-of-anti-neoplastic-immunotherapeutic-agents-associated-with-immune-dysregulation
#16
Laura L Cooling, John Sherbeck, Jonathon C Mowers, Sheri L Hugan
Ipilimumab, nivolumab, and pembrolizumab represent a new class of immunotherapeutic drugs for treating patients with advanced cancer. Known as checkpoint inhibitors, these drugs act to upregulate the cellular and humoral immune response to tumor antigens by inhibiting T-cell autoregulation. As a consequence, they can be associated with immune-related adverse events (irAEs) due to loss of self-tolerance, including rare cases of immune-related cytopenias. We performed a retrospective clinical chart review, including serologic, hematology, and chemistry laboratory results, of two patients who developed red blood cell (RBC) autoantibodies during treatment with a checkpoint inhibitor...
January 2017: Immunohematology
https://www.readbyqxmd.com/read/28425263/combination-therapy-with-dendritic-cell-based-vaccine-and-anti-cd69-antibody-enhances-antitumor-efficacy-in-renal-cell-carcinoma-bearing-mice
#17
Si-Ming Wei, Hang-Li Pan, Li Wang, Guo-Li Yin, Kai Zhong, Ya Zhou, Shu-Jiao Yang, Zhao-Liang Xin
BACKGROUND/AIM: Dendritic cell-based vaccine therapy for renal cell carcinoma is effective but requires improvement. Here we explored whether combination therapy with dendritic cell-based vaccine and anti-CD69 antibody can enhance antitumor efficacy in renal cell carcinoma-bearing mice. MATERIALS AND METHODS: Balb/c mice were challenged subcutaneously with murine renal cell carcinoma (Renca) cells. On day 3 after tumor cell inoculation, tumor-bearing mice either were left untreated or were treated with Renca tumor lysate-pulsed dendritic cells (i...
April 18, 2017: Turkish Journal of Medical Sciences
https://www.readbyqxmd.com/read/28423693/enhanced-anti-tumor-therapeutic-efficacy-of-dna-vaccine-by-fusing-the-e7-gene-to-baff-in-treating-human-papillomavirus-associated-cancer
#18
Chao-Chih Wu, Fang-Cih Wu, Yun-Tin Hsu, Yu-Chia Hsiao, Yuh-Cheng Yang, C Allen Chang, Chih-Long Chang
B-cell-activating factor (BAFF) belongs to the tumor necrosis factor family that not only stimulates B and T cells but also counteracts immune tolerance. BAFF is also a type II membrane protein, which is secreted through the endoplasmic reticulum (ER)-Golgi apparatus pathway. Fusing an antigen to BAFF might enhance the presentation of major histocompatibility complex class I molecules. These characteristics represent an opportunity to enhance the antitumor effects of DNA vaccines. Therefore, we fused BAFF to human papillomavirus type 16 E7 as a DNA vaccine and evaluated its antitumor effects...
March 9, 2017: Oncotarget
https://www.readbyqxmd.com/read/28423678/influence-of-ipilimumab-on-expanded-tumour-derived-t-cells-from-patients-with-metastatic-melanoma
#19
Jon Bjoern, Rikke Lyngaa, Rikke Andersen, Lisbet Hölmich Rosenkrantz, Sine Reker Hadrup, Marco Donia, Inge Marie Svane
INTRODUCTION: Tumour infiltrating lymphocyte (TIL) based adoptive cell therapy (ACT) is a promising treatment for patients with advanced melanoma. Retrospective studies suggested an association between previous treatment with anti-CTLA-4 antibodies and long term survival after subsequent ACT. Thus, we hypothesized that treatment with anti-CTLA-4 antibodies can induce favourable changes to be detected in TILs. RESULTS: Expanded T cells from Ipilimumab treated patients had a higher proportion of cells expressing CD27, intracellular CTLA-4, TIM-3 and LAG-3...
March 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/28421385/in-vitro-and-in-vivo-anti-tumor-effects-of-selected-platinum-iv-and-dinuclear-platinum-ii-complexes-against-lung-cancer-cells
#20
Milos Arsenijevic, Marija Milovanovic, Snezana Jovanovic, Natalija Arsenijevic, Bojana Simovic Markovic, Marina Gazdic, Vladislav Volarevic
In the present study, cytotoxic effects of cisplatin, the most usually used chemotherapeutic agent, were compared with new designed platinum(IV) ([PtCl4(en)] (en = ethylenediamine) and [PtCl4(dach)]) (dach = (±)-trans-1,2-diaminocyclohexane) and platinum(II) complexes ([{trans-Pt(NH3)2Cl}2(μ-pyrazine)](ClO4)2 (Pt1), [{trans-Pt(NH3)2Cl}2(μ-4,4'-bipyridyl)](ClO4)2DMF(Pt2),[{trans-Pt(NH3)2Cl}2(μ-1,2-bis(4pyridyl)ethane)](ClO4)2 (Pt3)), in vitro and in vivo against human and murine lung cancer cells, to determine anti-tumor potential of newly synthesized platinum-based drugs in the therapy of lung cancer...
April 18, 2017: Journal of Biological Inorganic Chemistry: JBIC
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