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https://www.readbyqxmd.com/read/29345636/promoting-the-accumulation-of-tumor-specific-t-cells-in-tumor-tissues-by-dendritic-cell-vaccines-and-chemokine-modulating-agents
#1
Nataša Obermajer, Julie Urban, Eva Wieckowski, Ravikumar Muthuswamy, Roshni Ravindranathan, David L Bartlett, Pawel Kalinski
This protocol describes how to induce large numbers of tumor-specific cytotoxic T cells (CTLs) in the spleens and lymph nodes of mice receiving dendritic cell (DC) vaccines and how to modulate tumor microenvironments (TMEs) to ensure effective homing of the vaccination-induced CTLs to tumor tissues. We also describe how to evaluate the numbers of tumor-specific CTLs within tumors. The protocol contains detailed information describing how to generate a specialized DC vaccine with augmented ability to induce tumor-specific CTLs...
February 2018: Nature Protocols
https://www.readbyqxmd.com/read/29344995/activation-of-human-cd141-and-cd1c-dendritic-cells-in-vivo-with-combined-tlr-3-and-tlr-7-8-ligation
#2
Frances E Pearson, Karshing Chang, Yoshihito Minoda, Ingrid M Leal Rojas, Oscar L Haigh, Ghazal Daraj, Kirsteen M Tullett, Kristen J Radford
Mice reconstituted with human hematopoietic stem cells are valuable models to study aspects of the human immune system in vivo. We describe a humanized mouse model (hu mice) in which fully functional human CD141+ and CD1c+ myeloid and CD123+ plasmacytoid dendritic cells (DC) develop from human cord blood CD34+ cells in immunodeficient mice. CD141+ DC are the human equivalents of murine CD8+ /CD103+ DC which are essential for the induction of tumor-inhibitory cytotoxic T lymphocyte (CTL) responses, making them attractive targets to exploit for the development of new cancer immunotherapies...
January 18, 2018: Immunology and Cell Biology
https://www.readbyqxmd.com/read/29344312/an-endogenous-vaccine-based-on-fluorophores-and-multivalent-immunoadjuvants-regulates-tumor-micro-environment-for-synergistic-photothermal-and-immunotherapy
#3
Ling Li, Suleixin Yang, Linjiang Song, Yan Zeng, Tao He, Ning Wang, Chuan Yu, Tao Yin, Li Liu, Xiawei Wei, Qinjie Wu, Yuquan Wei, Li Yang, Changyang Gong
Recently, near-infrared (NIR) light-based photothermal therapy (PTT) has been widely applied in cancer treatment. However, in most cases, the tissue penetration depth of NIR light is not sufficient and thus photothermal therapy is unable to completely eradicate deep, seated tumors inevitably leading to recurrence of the tumor. Due to this significant limitation of NIR, improved therapeutic strategies are urgently needed. Methods: We developed an endogenous vaccine based on a novel nanoparticle platform for combinatorial photothermal ablation and immunotherapy...
2018: Theranostics
https://www.readbyqxmd.com/read/29344283/antigen-presentation-of-the-oct4-and-sox2-peptides-by-cd154-activated-b-lymphocytes-enhances-the-killing-effect-of-cytotoxic-t-lymphocytes-on-tumor-stem-like-cells-derived-from-cisplatin-resistant-lung-cancer-cells
#4
Xueyan Zhang, Yanwei Zhang, Jianlin Xu, Huimin Wang, Xiaoxuan Zheng, Yuqing Lou, Baohui Han
The present study investigated whether antigen presentation of the Oct4 and Sox2 peptides by CD154-activated B lymphocytes can enhance the killing effect of CD8+ cytotoxic T lymphocytes (CTLs) on lung stem-like cancer cells (SLCCs). The CTLs were generated using an accelerated co-cultured dendritic cells (DC) (acDC) assay by incubating human peripheral blood mononuclear cells (PBMCs) from non-small-cell lung cancer patients with antigen peptides of Oct4 and Sox2 in the presence of several DC-activating agents...
2018: Journal of Cancer
https://www.readbyqxmd.com/read/29344274/immunotherapy-of-patient-with-hepatocellular-carcinoma-using-cytotoxic-t-lymphocytes-ex-vivo-activated-with-tumor-antigen-pulsed-dendritic-cells
#5
Ying Wang, Xijing Yang, Yi Yu, Zenghui Xu, Yan Sun, Hui Liu, Jingbo Cheng, Min Liu, Bibo Sha, Linfang Li, Na Ding, Zhong Li, Huajun Jin, Qijun Qian
Purpose The aim of this study was to evaluate the clinical response of immunotherapy with dendritic cell-cytotoxic T lymphocytes (DC-CTLs) in patients with hepatocellular carcinoma (HCC). Method Sixty-eight patients with a confirmed diagnosis of HCC and who received follow-up until December 2015 were enrolled. We measured immune phenotypes of DCs and activated T cells using flow cytometry and clinical indexes using an electrochemiluminescence method. Results DCs exhibited up-regulation of the maturation markers CD83, CD80, CD11c, and CD86 on day8...
2018: Journal of Cancer
https://www.readbyqxmd.com/read/29343444/activation-of-p53-in-immature-myeloid-precursor-cells-controls-differentiation-into-ly6c-cd103-monocytic-antigen-presenting-cells-in-tumors
#6
Madhav D Sharma, Paulo C Rodriguez, Brent H Koehn, Babak Baban, Yan Cui, Gang Guo, Michiko Shimoda, Rafal Pacholczyk, Huidong Shi, Eun-Joon Lee, Hongyan Xu, Theodore S Johnson, Yukai He, Taha Mergoub, Christopher Venable, Vincenzo Bronte, Jedd D Wolchok, Bruce R Blazar, David H Munn
CD103+ dendritic cells are critical for cross-presentation of tumor antigens. Here we have shown that during immunotherapy, large numbers of cells expressing CD103 arose in murine tumors via direct differentiation of Ly6c+ monocytic precursors. These Ly6c+CD103+ cells could derive from bone-marrow monocytic progenitors (cMoPs) or from peripheral cells present within the myeloid-derived suppressor cell (MDSC) population. Differentiation was controlled by inflammation-induced activation of the transcription factor p53, which drove upregulation of Batf3 and acquisition of the Ly6c+CD103+ phenotype...
January 16, 2018: Immunity
https://www.readbyqxmd.com/read/29343441/modcs-less-problems
#7
Alycia Gardner, Brian Ruffell
Type 1 conventional dendritic cells are necessary for the development of anti-tumor immunity. In this issue of Immunity, Sharma et al. (2018) identify a phenotypically similar monocyte-derived population within inflamed tumors that promotes T cell responses during therapy.
January 16, 2018: Immunity
https://www.readbyqxmd.com/read/29343435/paracrine-wnt5a-%C3%AE-catenin-signaling-triggers-a-metabolic-program-that-drives-dendritic-cell-tolerization
#8
Fei Zhao, Christine Xiao, Kathy S Evans, Tbalamayooran Theivanthiran, Nicholas DeVito, Alisha Holtzhausen, Juan Liu, Xiaojing Liu, David Boczkowski, Smita Nair, Jason W Locasale, Brent A Hanks
Despite recent advances, many cancers remain refractory to available immunotherapeutic strategies. Emerging evidence indicates that the tolerization of local dendritic cells (DCs) within the tumor microenvironment promotes immune evasion. Here, we have described a mechanism by which melanomas establish a site of immune privilege via a paracrine Wnt5a-β-catenin-peroxisome proliferator-activated receptor-γ (PPAR-γ) signaling pathway that drives fatty acid oxidation (FAO) in DCs by upregulating the expression of the carnitine palmitoyltransferase-1A (CPT1A) fatty acid transporter...
January 16, 2018: Immunity
https://www.readbyqxmd.com/read/29340095/tumoral-immune-infiltrate-if-pd-l1-expression-and-role-of-cd8-tia-1-lymphocytes-in-localized-osteosarcoma-patients-treated-within-protocol-isg-os1
#9
Emanuela Palmerini, Claudio Agostinelli, Piero Picci, Stefano Pileri, Teresa Marafioti, Pier-Luigi Lollini, Katia Scotlandi, Alessandra Longhi, Maria Serena Benassi, Stefano Ferrari
Background: We hypothesized that immune-infiltrates were associated with superior survival, and examined a primary osteosarcoma tissue microarrays (TMAs) to test this hypothesis. Methods: 129 patients (pts) with localized osteosarcoma treated within protocol ISG-OS1 were included in the study. Clinical characteristics, expression of CD8, CD3, FOXP3, CD20, CD68/CD163 (tumor associated macrophage, TAM), Tia-1 (cytotoxic T cell), CD303 (plasmacytoid dendritic cells: pDC), Arginase-1 (myeloid derived suppressor cells: MDSC), PD-1 on immune-cells (IC), and PD-L1 on tumoral cells (TC) and IC were analysed and correlated with outcome...
December 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/29339187/doxorubicin-loaded-dendritic-fe3o4-supramolecular-nanoparticles-for-magnetic-drug-targeting-and-tumor-regression-in-spheroid-murine-melanoma-model
#10
Saumya Nigam, D Bahadur
This work evaluates the magnetically-guided delivery of DOX-loaded dendritic-Fe3O4 nanoparticles and their tumor regression efficacy in subcutaneous melanoma in C57BL/6 mice. The hematological, biochemical and histopathological parameters were minimally affected. The nanoparticles localized in lungs, liver and spleen suggesting non-specific uptake. However, in tumor-bearing mice, substantially higher localization in magnetically-targeted tumor was observed when compared to passive localization in non-targeted tumor...
January 12, 2018: Nanomedicine: Nanotechnology, Biology, and Medicine
https://www.readbyqxmd.com/read/29339155/truncated-cd200-stimulates-tumor-immunity-leading-to-fewer-lung-metastases-in-a-novel-wistar-rat-metastasis-model
#11
Jun Kuwabara, Akihiro Umakoshi, Naoki Abe, Yutaro Sumida, Shota Ohsumi, Eika Usa, Kana Taguchi, Mohammed E Choudhury, Hajime Yano, Shirabe Matsumoto, Takeharu Kunieda, Hisaaki Takahashi, Toshihiro Yorozuya, Yuji Watanabe, Junya Tanaka
CD200 mediates immunosuppression in immune cells that express its receptor, CD200R. There are two CD200 variants; truncated CD200 that lacks the N-terminal sequence necessary for CD200R binding (CD200S) and full-length CD200 (CD200L). We established a novel lung metastasis model by subcutaneously transplanting C6 glioma cells into the backs of neonatal Wistar rats. All transplanted rats developed large back tumors, nearly 90% of which bore lung metastases. To compare the effects of CD200S and CD200L on tumor immunity, CD200L (C6-L)- or CD200S (C6-S)-expressing C6 cells were similarly transplanted...
January 12, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29337305/host-expression-of-pd-l1-determines-efficacy-of-pd-l1-pathway-blockade-mediated-tumor-regression
#12
Heng Lin, Shuang Wei, Elaine M Hurt, Michael D Green, Lili Zhao, Linda Vatan, Wojciech Szeliga, Ronald Herbst, Paul W Harms, Leslie A Fecher, Pankaj Vats, Arul M Chinnaiyan, Christopher D Lao, Theodore S Lawrence, Max Wicha, Junzo Hamanishi, Masaki Mandai, Ilona Kryczek, Weiping Zou
Programmed death-1 receptor (PD-L1, B7-H1) and programmed cell death protein 1 (PD-1) pathway blockade is a promising therapy for treating cancer. However, the mechanistic contribution of host and tumor PD-L1 and PD-1 signaling to the therapeutic efficacy of PD-L1 and PD-1 blockade remains elusive. Here, we evaluated 3 tumor-bearing mouse models that differ in their sensitivity to PD-L1 blockade and demonstrated a loss of therapeutic efficacy of PD-L1 blockade in immunodeficient mice and in PD-L1- and PD-1-deficient mice...
January 16, 2018: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/29334915/monitoring-the-responsiveness-of-t-and-antigen-presenting-cell-compartments-in-breast-cancer-patients-is-useful-to-predict-clinical-tumor-response-to-neoadjuvant-chemotherapy
#13
David A Bernal-Estévez, Oscar García, Ramiro Sánchez, Carlos A Parra-López
BACKGROUND: Vaccination of mice with tumors treated with Doxorubicin promotes a T cell immunity that relies on dendritic cell (DC) activation and is responsible for tumor control in vaccinated animals. Despite Doxorubicin in combination with Cyclophosphamide (A/C) is widely used to treat breast cancer patients, the stimulating effect of A/C on T and APC compartments and its correlation with patient's clinical response remains to be proved. METHODS: In this prospective study, we designed an in vitro system to monitor various immunological readouts in PBMCs obtained from a total of 17 breast cancer patients before, and after neoadjuvant anti-tumor therapy with A/C...
January 15, 2018: BMC Cancer
https://www.readbyqxmd.com/read/29334492/anti-il-10-mediated-enhancement-of-antitumor-efficacy-of-a-dendritic-cell-targeting-mip3%C3%AE-gp100-vaccine-in-the-b16f10-mouse-melanoma-model-is-dependent-on-type-i-interferons
#14
James T Gordy, Kun Luo, Brian Francica, Charles Drake, Richard B Markham
The chemokine MIP3α (CCL20) binds to CCR6 on immature dendritic cells. Vaccines fusing MIP3α to gp100 have been shown to be effective in therapeutically reducing melanoma tumor burden and prolonging survival in a mouse model. Other studies have provided evidence that interleukin-10 (IL-10) neutralizing antibodies (αIL-10) enhance immunologic melanoma therapies by modulating the tolerogenic tumor microenvironment. In the current study, we have utilized the B16F10 syngeneic mouse melanoma model to demonstrate for the first time that a therapy neutralizing IL-10 enhances the antitumor efficacy of a MIP3α-gp100 DNA vaccine, leading to significantly smaller tumors, slower growing tumors, and overall increases in mouse survival...
January 12, 2018: Journal of Immunotherapy
https://www.readbyqxmd.com/read/29331323/regulation-of-inflammatory-factors-by-double-stranded-rna-receptors-in-breast-cancer-cells
#15
Amritha Venkatesh, Harika Nandigam, Maria Muccioli, Manindra Singh, Tiffany Loftus, Deana Lewis, Michelle Pate, Fabian Benencia
Malignant cells are not the only components of a tumor mass since other cells (e.g., fibroblasts, infiltrating leukocytes and endothelial cells) are also part of it. In combination with the extracellular matrix, all these cells constitute the tumor microenvironment. In the last decade the role of the tumor microenvironment in cancer progression has gained increased attention and prompted efforts directed to abrogate its deleterious effects on anti-cancer therapies. The immune system can detect and attack tumor cells, and tumor-infiltrating lymphocytes (particularly CD8 T cells) have been associated with improved survival or better response to therapies in colorectal, melanoma, breast, prostate and ovarian cancer patients among others...
November 22, 2017: Immunobiology
https://www.readbyqxmd.com/read/29331266/human-papilloma-virus-specific-t-cells-can-be-generated-from-na%C3%A3-ve-t-cells-for-use-as-an-immunotherapeutic-strategy-for-immunocompromised-patients
#16
Sarah E McCormack, Conrad Russell Y Cruz, Kaylor E Wright, Allison B Powell, Haili Lang, Cornelia Trimble, Michael D Keller, Ephraim Fuchs, Catherine M Bollard
Human papilloma virus (HPV) is a known cause of cervical cancer, squamous cell carcinoma and laryngeal cancer. Although treatments exist for HPV-associated malignancies, patients unresponsive to these therapies have a poor prognosis. Recent findings from vaccine studies suggest that T-cell immunity is essential for disease control. Because Epstein-Barr Virus (EBV)-specific T cells have been highly successful in treating or preventing EBV-associated tumors, we hypothesized that the development of a manufacturing platform for HPV-specific T cells from healthy donors could be used in a third-party setting to treat patients with high-risk/relapsed HPV-associated cancers...
January 10, 2018: Cytotherapy
https://www.readbyqxmd.com/read/29330750/immunologic-and-gene-expression-profiles-of-spontaneous-canine-oligodendrogliomas
#17
Anna Filley, Mario Henriquez, Tanmoy Bhowmik, Brij Nath Tewari, Xi Rao, Jun Wan, Margaret A Miller, Yunlong Liu, R Timothy Bentley, Mahua Dey
Malignant glioma (MG), the most common primary brain tumor in adults, is extremely aggressive and uniformly fatal. Several treatment strategies have shown significant preclinical promise in murine models of glioma; however, none have produced meaningful clinical responses in human patients. We hypothesize that introduction of an additional preclinical animal model better approximating the complexity of human MG, particularly in interactions with host immune responses, will bridge the existing gap between these two stages of testing...
January 12, 2018: Journal of Neuro-oncology
https://www.readbyqxmd.com/read/29329556/cancer-immunotherapy-beyond-immune-checkpoint-inhibitors
#18
REVIEW
Julian A Marin-Acevedo, Aixa E Soyano, Bhagirathbhai Dholaria, Keith L Knutson, Yanyan Lou
Malignant cells have the capacity to rapidly grow exponentially and spread in part by suppressing, evading, and exploiting the host immune system. Immunotherapy is a form of oncologic treatment directed towards enhancing the host immune system against cancer. In recent years, manipulation of immune checkpoints or pathways has emerged as an important and effective form of immunotherapy. Agents that target cytotoxic T lymphocyte-associated molecule-4 (CTLA-4), programmed cell death receptor-1 (PD-1), and programmed cell death ligand-1 (PD-L1) are the most widely studied and recognized...
January 12, 2018: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/29325699/co-delivery-of-tumor-antigen-and-dual-toll-like-receptor-ligands-into-dendritic-cell-by-silicon-microparticle-enables-efficient-immunotherapy-against-melanoma
#19
Motao Zhu, Xilai Ding, Ruifang Zhao, Xuewu Liu, Haifa Shen, Chunmei Cai, Mauro Ferrari, Helen Y Wang, Rong-Fu Wang
Despite the importance and promise of cancer vaccines for broader prevention and treatment of cancer, limited clinical responses are observed, suggesting that key rational designs are required for inducing potent immune responses against cancer. Here we report a mesoporous silicon vector (MSV) as a multi-functional microparticle for formulating an efficient cancer vaccine composed of B16 melanoma derived-tyrosinase related protein 2 (TRP2) peptide and dual toll-like receptor (TLR) agonists. We demonstrated that MSV microparticles protected the peptide from rapid degradation for prolonged antigen presentation to immune cells...
January 8, 2018: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/29324304/injectable-polypeptide-hydrogel-for-dual-delivery-of-antigen-and-tlr3-agonist-to-modulate-dendritic-cells-in%C3%A2-vivo-and-enhance-potent-cytotoxic-t-lymphocyte-response-against-melanoma
#20
Huijuan Song, Pingsheng Huang, Jinfeng Niu, Gaona Shi, Chuangnian Zhang, Deling Kong, Weiwei Wang
Transplantation of immune cells manipulated in vitro to dictate immune responses in the body is promising in cancer immunotherapy. However, this approach suffers from low cell survival after administration, insufficient cell homing to lymph nodes, and off-target. Here we demonstrate an injectable and self-assembled poly(l-valine) hydrogel as the delivery carrier of cargoes including antigen and immunopotentiator for DCs modulation. Our results indicate the vaccine formulation composed of tumor cell lysates (TCL), TLR3 agonist, poly(I:C) and polypeptide hydrogel can robustly recruit, activate and mature DCs in vitro and in vivo by sustained release of TCL and poly(I:C)...
January 3, 2018: Biomaterials
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