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Anti-tumor T cell response

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https://www.readbyqxmd.com/read/28646491/sickle-cells-produce-functional-immune-modulators-and-cytotoxics
#1
Chiao-Wang Sun, Li-Chen Wu, Peter L Knopick, David S Bradley, Tim Townes, David S Terman
Sickle erythrocytes' (SSRBCs) unique physical adaptation to hypoxic conditions renders them able to home to hypoxic tumor niches in vivo, shut down tumor blood flow and induce tumoricidal responses. SSRBCs are also useful vehicles for transport of encapsulated drugs and oncolytic virus into hypoxic tumors with enhanced anti-tumor effects. In search of additional modes for arming sickle cells with cytotoxics, we turned to a lentiviral β-globin vector with optimized Locus Control Region/β-globin coding region/promoter/enhancers...
June 24, 2017: American Journal of Hematology
https://www.readbyqxmd.com/read/28646041/concurrent-ox40-and-cd30-ligand-blockade-abrogates-the-cd4-driven-autoimmunity-associated-with-ctla4-and-pd1-blockade-while-preserving-excellent-anti-cd8-tumor-immunity
#2
Maher G Nawaf, Maria H Ulvmar, David R Withers, Fiona M McConnell, Fabrina M Gaspal, Gwilym J Webb, Nick D Jones, Hideo Yagita, James P Allison, Peter J L Lane
Although strategies that block FOXP3-dependent regulatory T cell function (CTLA4 blockade) and the inhibitory receptor PD1 have shown great promise in promoting antitumor immune responses in humans, their widespread implementation for cancer immunotherapy has been hampered by significant off-target autoimmune side effects that can be lethal. Our work has shown that absence of OX40 and CD30 costimulatory signals prevents CD4 T cell-driven autoimmunity in Foxp3-deficient mice, suggesting a novel way to block these side effects...
June 23, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28644608/targeting-cpg-adjuvant-to-lymph-node-via-dextran-conjugate-enhances-anti-tumor-immunotherapy
#3
Weidong Zhang, Myunggi An, Jingchao Xi, Haipeng Liu
Nucleic acids based adjuvants recognized by Toll-like receptors (TLR) are potent immune system stimulants that can augment the anti-tumor immune responses in an antigen-specific manner. However, their clinical uses as vaccine adjuvants are limited primarily due to lack of accumulation in the lymph nodes, the anatomic sites where the immune responses are initiated. Here, we showed that chemical conjugation of type B CpG DNA, a TLR9 agonist to dextran polymer dramatically enhanced CpG's lymph node accumulation in mice...
June 23, 2017: Bioconjugate Chemistry
https://www.readbyqxmd.com/read/28644433/ctla-4-mediated-posttranslational-modifications-direct-cytotoxic-t-lymphocyte-differentiation
#4
Holger Lingel, Josef Wissing, Aditya Arra, Denny Schanze, Stefan Lienenklaus, Frank Klawonn, Mandy Pierau, Martin Zenker, Lothar Jänsch, Monika C Brunner-Weinzierl
The blockade of inhibitory receptors such as CTLA-4 (CD152) is being used as immune-checkpoint therapy, offering a powerful strategy to restore effective immune responses against tumors. To determine signal components that are induced under the control of CTLA-4 we analyzed activated murine CD8(+) T cells by quantitative proteomics. Accurate mass spectrometry revealed that CTLA-4 engagement led to central changes in the phosphorylation of proteins involved in T-cell differentiation. Beside other targets, we discovered a CTLA-4-mediated induction of the translational inhibitor programmed cell death-4 (PDCD4) as a result of FoxO1 nuclear re-localization...
June 23, 2017: Cell Death and Differentiation
https://www.readbyqxmd.com/read/28642820/intratumorally-injected-pro-inflammatory-allogeneic-dendritic-cells-as-immune-enhancers-a-first-in-human-study-in-unfavourable-risk-patients-with-metastatic-renal-cell-carcinoma
#5
Anna Laurell, Maria Lönnemark, Einar Brekkan, Anders Magnusson, Anna Tolf, Anna Carin Wallgren, Bengt Andersson, Lars Adamson, Rolf Kiessling, Alex Karlsson-Parra
BACKGROUND: Accumulating pre-clinical data indicate that the efficient induction of antigen-specific cytotoxic CD8+ T cells characterizing viral infections is caused by cross-priming where initially infected DCs produce an unique set of inflammatory factors that recruit and activate non-infected bystander DCs. Our DC-based immunotherapy concept is guided by such bystander view and accordingly, we have developed a cellular adjuvant consisting of pre-activated allogeneic DCs producing high levels of DC-recruiting and DC-activating factors...
2017: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/28642246/modulation-of-endoplasmic-reticulum-stress-controls-cd4-t-cell-activation-and-anti-tumor-function
#6
Jessica E Thaxton, Caroline Wallace, Brian Riesenberg, Yongliang Zhang, Chrystal Paulos, Craig Beeson, Bei Liu, Zihai Li
The endoplasmic reticulum (ER) is an energy-sensing organelle with intimate ties to programming cell activation and metabolic fate. T-cell receptor (TCR) activation represents a form of acute cell stress and induces mobilization of ER Ca(2+) stores. The role of the ER in programming T-cell activation and metabolic fate remains largely undefined. Gp96 is an ER protein with functions as a molecular chaperone and Ca(2+) buffering protein. We hypothesized that the ER stress response may be important for CD4(+) T-cell activation and that gp96 may be integral to this process...
June 22, 2017: Cancer Immunology Research
https://www.readbyqxmd.com/read/28641561/induction-of-humoral-and-cellular-immune-responses-in-mice-by-multiepitope-vaccines-composing-of-both-t-and-b-lymphocyte-epitopes-of-mage-a3which-are-recombined-into-hbcag
#7
Qingxin Chen, Wenshu Li, Pengfei Wang, Huanyi Shao, Yujie Ding, Wenhuan Wang, Danwei Cen, Yiqi Cai, Xiangyang Xue, Lifang Zhang, Guanbao Zhu
MAGE-A3 is highly expressed in many kinds of malignant diseases, and considered to be an ideal candidate for anti-tumor vaccine. To improve the immunogenicity of epitopes of MAGE-A3, hepatitis B virus core antigen (HBcAg) was used as an immune-carrier by insertion epitopes at HBcAg major immunodominant region (HBcAg(MIR)). In present study, we designed three kinds of MAGE-A3 multiepitopes containing T and B-cell dominant epitope-rich peptides, and constructed three recombinant chimeras of HBcAg(MIR)/MAGE-A3(EPI-1), HBcAg(MIR)/MAGE-A3(EPI-2), and HBcAg(MIR)/MAGE-A3(EPI-3) with prokaryotic codon optimization...
June 20, 2017: Protein and Peptide Letters
https://www.readbyqxmd.com/read/28638937/anti-gitr-antibody-treatment-increases-tcr-repertoire-diversity-of-regulatory-but-not-effector-t-cells-engaged-in-the-immune-response-against-b16-melanoma
#8
Bozena Scirka, Edyta Szurek, Maciej Pietrzak, Grzegorz Rempala, Pawel Kisielow, Leszek Ignatowicz, Arkadiusz Miazek
Crosslinking of glucocorticoid-induced TNF family-related receptor (GITR) with agonist antibodies restores cancer immunity by enhancing effector T cell (Teff) responses while interfering with intra-tumor regulatory T cell (Treg) stability and/or accumulation. However, how anti-GITR antibody infusion changes T cell receptor (TCR) repertoire of Teffs and Tregs engaged in anti-tumor immune response is unclear. Here, we used a transgenic mouse model (TCRmini) where T cells express naturally generated but limited TCR repertoire to trace the fate of individual T cells recognizing B16 melanoma in tumor-bearing mice, treated or non-treated with an anti-GITR monoclonal antibody DTA-1...
June 21, 2017: Archivum Immunologiae et Therapiae Experimentalis
https://www.readbyqxmd.com/read/28638727/identification-of-an-immunogenic-neo-epitope-encoded-by-mouse-sarcoma-using-cxcr3-ligand-mrnas-as-sensors
#9
Keisuke Fujii, Yoshihiro Miyahara, Naozumi Harada, Daisuke Muraoka, Mitsuhiro Komura, Rui Yamaguchi, Hideo Yagita, Junko Nakamura, Sahoko Sugino, Satoshi Okumura, Seiya Imoto, Satoru Miyano, Hiroshi Shiku
The CXCR3 ligands CXCL9, 10, and 11 play critical roles in the amplification of immune responses by recruiting CXCR3(+) immune effector cells to the tumor site. Taking advantage of this property of CXCR3 ligands, we aimed to establish a novel approach to identify immunogenic mutated-antigens. We examined the feasibility of using CXCR3 ligand mRNAs as sensors for detection of specific immune responses in human and murine systems. We further investigated whether this approach is applicable for the identification of immunogenic mutated-antigens by using murine sarcoma lines...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28638725/administration-of-a-vasoactive-intestinal-peptide-antagonist-enhances-the-autologous-anti-leukemia-t-cell-response-in-murine-models-of-acute-leukemia
#10
Christopher T Petersen, Jian-Ming Li, Edmund K Waller
Vasoactive intestinal peptide (VIP) is a neuroendocrine peptide hormone that has potent anti-inflammatory activities. VIP signaling through its receptor VPAC1 on T cells leads to reduced proliferation and a reduction in pro-inflammatory cytokine secretion. We report here that inhibition of the VIP pathway with a peptide antagonist significantly enhances a T-cell-dependent, autologous anti-leukemia response in murine models of acute myeloid leukemia and T lymphoblastic leukemia. Subcutaneous administration of the VIP antagonist, VIPhyb, resulted in reduced tumor burden and significantly enhanced survival (30-50% survival) over vehicle-treated controls (0-20% survival)...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28638480/mouse-ip-10-gene-delivered-by-folate-modified-chitosan-nanoparticles-and-dendritic-tumor-cells-fusion-vaccine-effectively-inhibit-the-growth-of-hepatocellular-carcinoma-in-mice
#11
Zixi Hu, Jiaojiao Chen, Sufang Zhou, Nuo Yang, Siliang Duan, Zhenghua Zhang, Jing Su, Jian He, Zhiyong Zhang, Xiaoling Lu, Yongxiang Zhao
Dendritic cells (DC) and tumor cell fusion vaccine (DC/tumor cell fusion vaccine) is considered an effective approach in cancer biotherapy. However, its therapeutic effects in early clinical trials have been suboptimal partially due to the immunosuppressive tumor environment. In this study, we used nanoparticles of folate (FA)-modified chitosan, a non-viral vector capable of targeting tumor cells with high expression of FA receptors. FA-chitosan nanoparticles were used as biological carriers for the expression plasmid of the mouse interferon-induced protein-10 (mIP-10) gene, a potent chemoattractant for cytotoxic T cells...
2017: Theranostics
https://www.readbyqxmd.com/read/28637010/local-application-of-bacteria-improves-safety-of-salmonella-mediated-tumor-therapy-and-retains-advantages-of-systemic-infection
#12
Dino Kocijancic, Sebastian Felgner, Tim Schauer, Michael Frahm, Ulrike Heise, Kurt Zimmermann, Marc Erhardt, Siegfried Weiss
Cancer is a devastating disease and a large socio-economic burden. Novel therapeutic solutions are on the rise, although a cure remains elusive. Application of microorganisms represents an ancient therapeutic strategy, lately revoked and refined via simultaneous attenuation and amelioration of pathogenic properties. Salmonella Typhimurium has prevailed in preclinical development. Yet, using virulent strains for systemic treatment might cause severe side effects. In the present study, we highlight a modified strain based on Salmonella Typhimurium UK-1 expressing hexa-acylated Lipid A...
June 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/28633655/inhibition-of-mmp-2-and-mmp-9-decreases-cellular-migration-and-angiogenesis-in-in-vitro-models-of-retinoblastoma
#13
Anderson H Webb, Bradley T Gao, Zachary K Goldsmith, Andrew S Irvine, Nabil Saleh, Ryan P Lee, Justin B Lendermon, Rajini Bheemreddy, Qiuhua Zhang, Rachel C Brennan, Dianna Johnson, Jena J Steinle, Matthew W Wilson, Vanessa M Morales-Tirado
BACKGROUND: Retinoblastoma (Rb) is the most common primary intraocular tumor in children. Local treatment of the intraocular disease is usually effective if diagnosed early; however advanced Rb can metastasize through routes that involve invasion of the choroid, sclera and optic nerve or more broadly via the ocular vasculature. Metastatic Rb patients have very high mortality rates. While current therapy for Rb is directed toward blocking tumor cell division and tumor growth, there are no specific treatments targeted to block Rb metastasis...
June 20, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28629173/autophagic-mechanism-in-anti-cancer-immunity-its-pros-and-cons-for-cancer-therapy
#14
REVIEW
Ying-Ying Li, Lynn G Feun, Angkana Thongkum, Chiao-Hui Tu, Shu-Mei Chen, Medhi Wangpaichitr, Chunjing Wu, Macus T Kuo, Niramol Savaraj
Autophagy, a self-eating machinery, has been reported as an adaptive response to maintain metabolic homeostasis when cancer cells encounter stress. It has been appreciated that autophagy acts as a double-edge sword to decide the fate of cancer cells upon stress factors, molecular subtypes, and microenvironmental conditions. Currently, the majority of evidence support that autophagy in cancer cells is a vital mechanism bringing on resistance to current and prospective treatments, yet whether autophagy affects the anticancer immune response remains unclear and controversial...
June 19, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28628092/tissue-resident-memory-features-are-linked-to-the-magnitude-of-cytotoxic-t-cell-responses-in-human-lung-cancer
#15
Anusha-Preethi Ganesan, James Clarke, Oliver Wood, Eva M Garrido-Martin, Serena J Chee, Toby Mellows, Daniela Samaniego-Castruita, Divya Singh, Grégory Seumois, Aiman Alzetani, Edwin Woo, Peter S Friedmann, Emma V King, Gareth J Thomas, Tilman Sanchez-Elsner, Pandurangan Vijayanand, Christian H Ottensmeier
Therapies that boost the anti-tumor responses of cytotoxic T lymphocytes (CTLs) have shown promise; however, clinical responses to the immunotherapeutic agents currently available vary considerably, and the molecular basis of this is unclear. We performed transcriptomic profiling of tumor-infiltrating CTLs from treatment-naive patients with lung cancer to define the molecular features associated with the robustness of anti-tumor immune responses. We observed considerable heterogeneity in the expression of molecules associated with activation of the T cell antigen receptor (TCR) and of immunological-checkpoint molecules such as 4-1BB, PD-1 and TIM-3...
June 19, 2017: Nature Immunology
https://www.readbyqxmd.com/read/28626234/b-cell-regulation-in-cancer-and-anti-tumor-immunity
#16
REVIEW
Anushruti Sarvaria, J Alejandro Madrigal, Aurore Saudemont
The balance between immune effector cells and immunosuppressive cells and how this regulates the tumor microenvironment has been well described. A significant contribution of immune regulatory cells, including regulatory T cells, to tumor progression has been widely reported. An emerging body of evidence has recently recognized a role for B cells in modulating the immune response to tumors and lymphoid malignancies. Regulatory B cells (Bregs) are a newly designated subset of B cells that have been shown to play a pivotal role in regulating immune responses involved in inflammation, autoimmunity and, more recently, cancer...
June 19, 2017: Cellular & Molecular Immunology
https://www.readbyqxmd.com/read/28626216/therapeutic-effects-of-csf1r-blocking-antibodies-in-multiple-myeloma
#17
Q Wang, Y Lu, R Li, Y Jiang, Y Zheng, J Qian, E Bi, C Zhang, J Hou, S Wang, Q Yi
Our previous studies showed that macrophages (MФs), especially myeloma-associated MФs (MAMs) induce chemoresistance in human myeloma. Here we explored the potential of targeting MФs, by using colony-stimulating factor 1 receptor (CSF1R)-blocking mAbs, to treat myeloma. Our results showed that CSF1R blockade specifically inhibited the differentiation, proliferation and survival of murine M2 MФs and MAMs, and repolarized MAMs towards M1-like MФs in vitro. CSF1R blockade alone inhibited myeloma growth in vivo, by partially depleting MAMs, polarizing MAMs to the M1 phenotype, and inducing a tumor-specific cytotoxic CD4(+) T cell response...
June 19, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28624449/intratumoral-injection-of-ifn-%C3%AE-induces-chemokine-production-in-melanoma-and-augments-the-therapeutic-efficacy-of-anti-pd-l1-mab
#18
Jiro Uehara, Takayuki Ohkuri, Akemi Kosaka, Kei Ishibashi, Yui Hirata, Kenzo Ohara, Toshihiro Nagato, Kensuke Oikawa, Naoko Aoki, Yasuaki Harabuchi, Akemi Ishida-Yamamoto, Hiroya Kobayashi
Despite recent advances in treatment for melanoma patients through using immune checkpoint inhibitors, these monotherapies have limitations and additional treatments have been explored. Type I IFNs have been used to treat melanoma and possess immunomodulatory effects including enhancement of T-cell infiltration. T-cell plays a critical role in immune checkpoint therapies via restoration of effector functions and tumor infiltration by T-cells predicts longer survival in a variety of cancer types. Moreover, tumor-infiltrating T-cells are associated with the expression of chemokines such as CCL5 and CXCR3 ligands in tumor tissues...
June 14, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28624137/effect-of-tlr-ligands-co-encapsulated-with-multiepitopic-antigen-in-nanoliposomes-targeted-to-human-dcs-via-fc-receptor-for-cancer-vaccines
#19
Felix Rueda, Christina Eich, Begoña Cordobilla, Pere Domingo, Gerardo Acosta, Fernando Albericio, Luis J Cruz, Joan C Domingo
Nanoliposomes (NLs) hold promise as new highly specific nanomedicine for anti-tumor vaccines, since they could be targeted to specific receptors on dendritic cell (DC) to induce maturation and activation and increase the anti-tumor immune response. Here we studied a NLs formulation targeted or not to FcR (the receptor for the IgG Fc fragment) for the treatment of androgen-responsive prostate cancer. Luteinizing-hormone-releasing hormone (LHRH) peptide (B- and T-cell epitopes), in tandem with a tetanus toxoid T-helper epitope (830-844 region) and several TLR (Toll-Like Receptor) ligands as adjuvants were co-encapsulated...
June 10, 2017: Immunobiology
https://www.readbyqxmd.com/read/28623086/the-transcription-factor-t-bet-limits-amplification-of-type-i-ifn-transcriptome-and-circuitry-in-t-helper-1-cells
#20
Shigeru Iwata, Yohei Mikami, Hong-Wei Sun, Stephen R Brooks, Dragana Jankovic, Kiyoshi Hirahara, Atsushi Onodera, Han-Yu Shih, Takeshi Kawabe, Kan Jiang, Toshinori Nakayama, Alan Sher, John J O'Shea, Fred P Davis, Yuka Kanno
Host defense requires the specification of CD4(+) helper T (Th) cells into distinct fates, including Th1 cells that preferentially produce interferon-γ (IFN-γ). IFN-γ, a member of a large family of anti-pathogenic and anti-tumor IFNs, induces T-bet, a lineage-defining transcription factor for Th1 cells, which in turn supports IFN-γ production in a feed-forward manner. Herein, we show that a cell-intrinsic role of T-bet influences how T cells perceive their secreted product in the environment. In the absence of T-bet, IFN-γ aberrantly induced a type I IFN transcriptomic program...
June 20, 2017: Immunity
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