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https://www.readbyqxmd.com/read/28103506/the-effect-of-anti-angiogenic-drugs-on-regulatory-t-cells-in-the-tumor-microenvironment
#1
REVIEW
Chenxi Hu, Xiaodong Jiang
A benefit of anti-angiogenic drugs is improved tumor immune tolerance. Regulatory T cells (Tregs) in the tumor microenvironment mediate tumor immune tolerance and anti-angiogenic drugs not only indirectly affect Tregs via dendritic cells (DCs) and myeloid-derived suppressor cells (MDSCs) but they can also act directly on Tregs causing immunosuppression. Specifically, these drugs may induce differentiation and chemotaxis and reduce the number and function of Tregs by targeting vascular endothelial growth factor receptor 2 (VEGFR-2) and neuropilin-1 (NRP-1) on the cell surface...
January 16, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28099196/use-of-engineered-exosomes-expressing-hla-and-costimulatory-molecules-to-generate-antigen-specific-cd8-t-cells-for-adoptive-cell-therapy
#2
Sueon Kim, Hyun-Jung Sohn, Hyun-Joo Lee, Dae-Hee Sohn, Seung-Joo Hyun, Hyun-Il Cho, Tai-Gyu Kim
Dendritic cell-derived exosomes (DEX) comprise an efficient stimulator of T cells. However, the production of sufficient DEX remains a barrier to their broad applicability in immunotherapeutic approaches. In previous studies, genetically engineered K562 have been used to generate artificial antigen presenting cells (AAPC). Here, we isolated exosomes from K562 cells (referred to as CoEX-A2s) engineered to express human leukocyte antigen (HLA)-A2 and costimulatory molecules such as CD80, CD83, and 41BBL. CoEX-A2s were capable of stimulating antigen-specific CD8 T cells both directly and indirectly via CoEX-A2 cross-dressed cells...
January 17, 2017: Journal of Immunotherapy
https://www.readbyqxmd.com/read/28099147/ctla-4-positive-breast-cancer-cells-suppress-dendritic-cells-maturation-and-function
#3
Xi Chen, Qianqian Shao, Shengnan Hao, Zhonghua Zhao, Yang Wang, Xiaofan Guo, Ying He, Wenjuan Gao, Haiting Mao
Cytotoxic T lymphocyte-associated antigen 4 (CTLA-4), a potent immunoregulatory molecule, can down-regulate T-cell activation and inhibit anti-tumor immune response. This study showed that LPS-stimulated human dendritic cells (DCs) decreased the expression of HLA-DR, CD83 and costimulatory molecules (CD40, CD80 and CD86) following coculturing with CTLA-4+ breast cancer cells. Moreover, the suppressed DCs further inhibited proliferation of allogeneic CD4+/CD8+ T-cells, differentiation of Th1 and function of cytotoxic lymphocytes (CTLs)...
January 13, 2017: Oncotarget
https://www.readbyqxmd.com/read/28099143/desirable-cytolytic-immune-effector-cell-recruitment-by-interleukin-15-dendritic-cells
#4
Heleen H Van Acker, Ottavio Beretta, Sébastien Anguille, Lien De Caluwé, Angela Papagna, Johan M Van den Bergh, Yannick Willemen, Herman Goossens, Zwi N Berneman, Viggo F Van Tendeloo, Evelien L Smits, Maria Foti, Eva Lion
Success of dendritic cell (DC) therapy in treating malignancies is depending on the DC capacity to attract immune effector cells, considering their reciprocal crosstalk is partially regulated by cell-contact-dependent mechanisms. Although critical for therapeutic efficacy, immune cell recruitment is a largely overlooked aspect regarding optimization of DC vaccination. In this paper we have made a head-to-head comparison of interleukin (IL)-15-cultured DCs and conventional IL-4-cultured DCs with regard to their proficiency in the recruitment of (innate) immune effector cells...
January 13, 2017: Oncotarget
https://www.readbyqxmd.com/read/28098734/multimodal-fundus-imaging-of-outer-retinal-tubulations-in-choroidal-osteoma-patients
#5
Yi Xuan, Yongjin Zhang, Min Wang, Jinli Guo, Lei Li, Wei Liu, Xiaofeng Ye
PURPOSE: To evaluate the morphological findings of outer retinal tubulations (ORTs) shown on multimodal imaging modalities in patients with choroidal osteoma. METHODS: Nineteen eyes of 17 patients with choroidal osteoma underwent full clinical and imaging assessments. Color fundus photography, spectral-domain optical coherence tomography (OCT), and en face OCT were used to identify and detect the characteristics of ORT structures, including the shape, configuration, location, and distribution in the fundus...
January 16, 2017: Retina
https://www.readbyqxmd.com/read/28098061/prostate-cancer-immunotherapy-particularly-in-combination-with-androgen-deprivation-or-radiation-treatment-customized-pharmacogenomic-approaches-to-overcome-immunotherapy-cancer-resistance
#6
REVIEW
C Alberti
Conventional therapeutic approaches for advanced prostate cancer - such as androgen deprivation, chemotherapy, radiation - come up often against lack of effectiveness because of possible arising of correlative cancer cell resistance and/or inadequate anti-tumor immune conditions. Whence the timeliness of resorting to immune-based treatment strategies including either therapeutic vaccination-based active immunotherapy or anti-tumor monoclonal antibody-mediated passive immunotherapy. Particularly attractive, as for research studies and clinical applications, results to be the cytotoxic T-lymphocyte check point blockade by the use of anti-CTLA-4 and PD-1 monoclonal antibodies, particularly when combined with androgen deprivation therapy or radiation...
September 2017: Il Giornale di Chirurgia
https://www.readbyqxmd.com/read/28096390/modification-of-host-dendritic-cells-by-microchimerism-derived-extracellular-vesicles-generates-split-tolerance
#7
William Bracamonte-Baran, Jonathan Florentin, Ying Zhou, Ewa Jankowska-Gan, W John Haynes, Weixiong Zhong, Todd V Brennan, Partha Dutta, Frans H J Claas, Jon J van Rood, William J Burlingham
Maternal microchimerism (MMc) has been associated with development of allospecific transplant tolerance, antitumor immunity, and cross-generational reproductive fitness, but its mode of action is unknown. We found in a murine model that MMc caused exposure to the noninherited maternal antigens in all offspring, but in some, MMc magnitude was enough to cause membrane alloantigen acquisition (mAAQ; "cross-dressing") of host dendritic cells (DCs). Extracellular vesicle (EV)-enriched serum fractions from mAAQ(+), but not from non-mAAQ, mice reproduced the DC cross-dressing phenomenon in vitro...
January 17, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28094582/effects-of-arsenic-on-porcine-dendritic-cells-in-vitro
#8
Jalil Mehrzad, Mohamad Hosein Mahmudy Gharaie, Masumeh Taheri
Exposure to arsenic (As) is an ongoing, and in some places increasing, health problem. Still, however, the effects of As exposure on the immune system are not well understood. Dendritic cells (DC) are a critical immune cell that bridges the innate and adaptive immune systems. To determine the impact of inorganic (i)As exposure on DC, the effects of (geo)anthropogenically relevant levels of NaAsO2 on the function of porcine monocyte-derived DC (MoDC) were evaluated in an in vitro model. The results showed a low dose of iAs reduced the phagocytic capacity of MoDC...
January 17, 2017: Journal of Immunotoxicology
https://www.readbyqxmd.com/read/28088065/methionine-enkephalin-menk-mounts-antitumor-effect-via-regulating-dendritic-cells-dcs
#9
Yiming Meng, Xinghua Gao, Wenna Chen, Nicolas P Plotnikoff, Noreen Griffin, Guirong Zhang, Fengping Shan
MENK, an endogenous opioid peptide has been reported to have many immunological and antitumor activities. So far the detailed mechanisms of antitumor through regulating DCs by MENK have not been elucidated yet. The aim of this work was to investigate the antitumor mechanisms of MENK via regulating DC. The monitoring methods, such as ELISA, MTS assay, CFSE, Real-time PCR and Western blot were included in our research. We found bone marrow derived dendritic cells (BMDCs) in 36 female C57BL/6 mice treated with MENK enhanced expression of key surface molecules, increased production of critical cytokines reduced endocytosis of FITC-dextran, upregulated TLR4 through MyD88/NF-κB signaling pathway and mounted higher antitumor activity...
January 11, 2017: International Immunopharmacology
https://www.readbyqxmd.com/read/28079009/emerging-roles-of-calreticulin-in-cancer-implications-for-therapy
#10
Kavya Venkateswaran, Amit Verma, Anant Narayan Bhatt, Anju Shrivastava, Kailash Manda, Hanumantharao G Raj, Ashok Prasad, Christophe Len, Virinder S Parmar, Bilikere Dwarakanath
Calreticulin (CRT), initially identified as a ubiquitous calcium-binding protein in the endoplasmic reticulum, has emerged as a multifunctional protein with roles in calcium homeostasis, molecular chaperoning and cell adhesion. Emerging evidence suggests its involvement in tumorigenesis facilitating proliferation, migration, and adhesion. CRT translocated to the cell surface (ecto-CRT) serves as a phagocytic signal for immunogenic cell death (ICD) mediated through dendritic cells (DCs) and cytotoxic T-cell activation thereby making tumors susceptible to immunotherapy-based anti-cancer strategies...
January 11, 2017: Current Protein & Peptide Science
https://www.readbyqxmd.com/read/28077213/inhibition-of-dopamine-receptor-d3-signaling-in-dendritic-cells-increases-antigen-cross-presentation-to-cd8-t-cells-favoring-anti-tumor-immunity
#11
Claudio Figueroa, Felipe Gálvez-Cancino, Cesar Oyarce, Francisco Contreras, Carolina Prado, Catalina Valeria, Sebastián Cruz, Alvaro Lladser, Rodrigo Pacheco
Dendritic cells (DCs) display the unique ability for cross-presenting antigens to CD8(+) T-cells, promoting their differentiation into cytotoxic T-lymphocytes (CTLs), which play a pivotal role in anti-tumor immunity. Emerging evidence points to dopamine receptor D3 (D3R) as a key regulator of immunity. Accordingly, we studied how D3R regulates DCs function in anti-tumor immunity. The results show that D3R-deficiency in DCs enhanced expansion of CTLs in vivo and induced stronger anti-tumor immunity. Co-culture experiments indicated that D3R-inhibition in DCs potentiated antigen cross-presentation and CTLs activation...
January 2, 2017: Journal of Neuroimmunology
https://www.readbyqxmd.com/read/28073842/expression-of-cd14-il-10-and-tolerogenic-signature-in-dendritic-cells-inversely-correlate-with-response-to-tarp-vaccination-in-prostate-cancer-patients
#12
Luciano Castiello, Marianna Sabatino, Jiaqiang Ren, Masaki Terabe, Hanh Khuu, Lauren V Wood, Jay A Berzofsky, David F Stroncek
PURPOSE: Despite the vast number of clinical trials conducted so far, Dendritic cell (DC)-based cancer vaccines have mostly shown unsatisfactory results. Factors and manufacturing procedures essential for these therapeutics to induce effective anti-tumor immune responses have yet to be fully characterized. We here aimed to identify DC markers correlating with clinical and immunological response in a prostate carcinoma vaccination regimen. EXPERIMENTAL DESIGN: We performed an extensive characterization of DCs used to vaccinate 18 prostate carcinoma patients enrolled in a pilot trial of TCR gamma alternate reading frame protein (TARP) peptide vaccination (NCT00908258)...
January 10, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28072560/a-prostacyclin-analog-cicaprost-exhibits-potent-anti-inflammatory-activity-in-human-primary-immune-cells-and-a-uveitis-model
#13
Jenny W Wang, Chau Vu, Neil J Poloso
PURPOSE: To investigate the therapeutic potential of a prostacyclin (IP) receptor agonist for ocular inflammation and the effect on immune cells. METHODS: The anti-inflammatory activities of cicaprost were determined in primary human monocyte-derived macrophages and human monocyte-derived dendritic cells (MoDC), as well as a lipopolysaccharides (LPS)-induced rat uveitis model. Multiple cytokine release was measured by utilizing Luminex Technology. Prostacyclin (IP) Receptor expression was detected by reverse transcription-polymerase chain receptor...
January 10, 2017: Journal of Ocular Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/28069806/dna-containing-exosomes-derived-from-cancer-cells-treated-with-topotecan-activate-a-sting-dependent-pathway-and-reinforce-antitumor-immunity
#14
Yuichi Kitai, Takumi Kawasaki, Takuya Sueyoshi, Kouji Kobiyama, Ken J Ishii, Jian Zou, Shizuo Akira, Tadashi Matsuda, Taro Kawai
Danger-associated molecular patterns derived from damaged or dying cells elicit inflammation and potentiate antitumor immune responses. In this article, we show that treatment of breast cancer cells with the antitumor agent topotecan (TPT), an inhibitor of topoisomerase I, induces danger-associated molecular pattern secretion that triggers dendritic cell (DC) activation and cytokine production. TPT administration inhibits tumor growth in tumor-bearing mice, which is accompanied by infiltration of activated DCs and CD8(+) T cells...
January 9, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28069554/encapsulation-of-two-different-tlr-ligands-into-liposomes-confer-protective-immunity-and-prevent-tumor-development
#15
Banu Bayyurt, Gizem Tincer, Kubra Almacioglu, Esin Alpdundar, Mayda Gursel, Ihsan Gursel
Nucleic acid-based Toll-like receptor (TLR) ligands are promising adjuvants and immunotherapeutic agents. Combination of TLR ligands potentiates immune response by providing synergistic immune activity via triggering different signaling pathways and may impact antigen dependent T-cell immune memory. However, their short circulation time due to nuclease attack hampers their clinical performance. Liposomes offer inclusion of protein and nucleic acid-based drugs with high encapsulation efficiency and drug loading...
January 7, 2017: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/28069362/ex-vivo-antigen-pulsed-pbmcs-generate-potent-and-long-lasting-immunity-to-infection-when-administered-as-a-vaccine
#16
Sudeep Kumar, Raju Sunagar, Giang Pham, Edmund J Gosselin, David Nalin
Numerous studies have demonstrated that administration of antigen (Ag)-pulsed dendritic cells (DCs) is an effective strategy for enhancing immunity to tumors and infectious disease organisms. However, the generation and/or isolation of DCs can require substantial time and expense. Therefore, using inactivated F. tularensis (iFt) Ag as a model immunogen, we first sought to determine if DCs could be replaced with peripheral blood mononuclear cells (PBMCs) during the ex-vivo pulse phase and still provide protection against Ft infection...
January 6, 2017: Vaccine
https://www.readbyqxmd.com/read/28060726/immunogenic-cancer-cell-death-selectively-induced-by-near-infrared-photoimmunotherapy-initiates-host-tumor-immunity
#17
Mikako Ogawa, Yusuke Tomita, Yuko Nakamura, Min-Jung Lee, Sunmin Lee, Saori Tomita, Tadanobu Nagaya, Kazuhide Sato, Toyohiko Yamauchi, Hidenao Iwai, Abhishek Kumar, Timothy Haystead, Hari Shroff, Peter L Choyke, Jane B Trepel, Hisataka Kobayashi
Immunogenic cell death (ICD) is a form of cell death that activates an adaptive immune response against dead-cell-associated antigens. Cancer cells killed via ICD can elicit antitumor immunity. ICD is efficiently induced by near-infrared photo-immunotherapy (NIR-PIT) that selectively kills target-cells on which antibody-photoabsorber conjugates bind and are activated by NIR light exposure. Advanced live cell microscopies showed that NIR-PIT caused rapid and irreversible damage to the cell membrane function leading to swelling and bursting, releasing intracellular components due to the influx of water into the cell...
January 2, 2017: Oncotarget
https://www.readbyqxmd.com/read/28060268/a-facile-and-efficient-approach-for-the-production-of-reversible-disulfide-cross-linked-micelles
#18
Yuanpei Li, Gaurav Bharadwaj, Joyce S Lee
Nanomedicine is an emerging form of therapy that harnesses the unique properties of particles that are nanometers in scale for biomedical application. Improving drug delivery to maximize therapeutic outcomes and to reduce drug-associated side effects are some of the cornerstones of present-day nanomedicine. Nanoparticles in particular have found a wide application in cancer treatment. Nanoparticles that offer a high degree of flexibility in design, application, and production based on the tumor microenvironment are projected to be more effective with rapid translation into clinical practice...
December 23, 2016: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/28060117/blastic-plasmocytoid-dendritic-cell-neoplasm-with-skin-and-myeloid-location
#19
Agnieszka Mizia-Malarz, Grażyna Sobol-Milejska
Blastic plasmocytoid dendritic cell neoplasm is one of the aggressive hematopoietic malignancy with predilection for the skin. It is a tumor derived from the plasmocytoid dendritic precursor cells. Skin is its most common location; however, it may also affect bone marrow, lymph nodes, or spleen. The condition is rarely diagnosed in children; so far only 36 cases have been reported. The diagnosis usually takes time and there are no uniform treatment guidelines. This paper presents a case of a 6-year-old boy with blastic plasmocytoid dendritic cell neoplasm (skin and myeloid location)...
January 5, 2017: Journal of Pediatric Hematology/oncology
https://www.readbyqxmd.com/read/28057175/pour-comprendre-l%C3%A2-activation-lymphocytaire-t
#20
Jeanne Galaine, Yann Godet, Olivier Adotévi
T cells activation is a finely regulated process to establish an effective anti-infectious or antitumor immune response while avoiding harmful autoimmune reactions. Although T cells are considered to be the main protagonists of the antitumor immune response, they act in interaction with other immune cells. The meeting of naive T cells with dendritic cells induces their differentiation into effector cells following the recognition of the peptide-MHC complex by the T cell receptor. The interaction of costimulatory molecules present on the surface of T cells with their ligand (s) expressed by mature dendritic cells contribute to the optimal T cell activation and to the formation of the immunological synapse...
November 2016: Bulletin du Cancer
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