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https://www.readbyqxmd.com/read/29764863/extracorporeal-photochemotherapy-drives-monocyte-to-dendritic-cell-maturation-to-induce-anti-cancer-immunity
#1
Alessandra Ventura, Aaron Vassall, Eve Robinson, Renata Filler, Douglas Hanlon, Katrina Meeth, Harib Ezaldein, Michael Girardi, Olga Sobolev, Marcus W Bosenberg, Richard L Edelson
Extracorporeal photochemotherapy (ECP) is a cancer immunotherapy for cutaneous T cell lymphoma (CTCL) operative in more than 350 centers worldwide. While its efficacy and favorable safety profile have driven its widespread use, elucidation of its underlying mechanism has been difficult. In this study, we identify the principal contributors to the anti-cancer immunotherapeutic effects of ECP, with the goal of enhancing potency and broadening applicability to additional malignancies. First, we scaled down the clinical ECP leukocyte-processing device to mouse size...
May 15, 2018: Cancer Research
https://www.readbyqxmd.com/read/29744449/dox-il-2-ifn-%C3%AE-co-loaded-thermo-sensitive-polypeptide-hydrogel-for-efficient-melanoma-treatment
#2
Qiang Lv, Chaoliang He, Fenli Quan, Shuangjiang Yu, Xuesi Chen
Melanoma has been a serious threat to the human health; however, effective therapeutic methods of this cancer are still limited. Combined local therapy is a crucial approach for achieving a superior anti-tumor efficacy. In this paper, a chemo-immunotherapy system of DOX, IL-2 and IFN-γ based on poly(γ-ethyl-L-glutamate)-poly(ethylene glycol)-poly(γ-ethyl-L-glutamate) (PELG-PEG-PELG) hydrogel was developed for local treatment of melanoma xenograft. The drug release process of this system exhibited a short term of burst release (the first 3 days), followed by a long-term sustained release (the following 26 days)...
March 2018: Bioactive Materials
https://www.readbyqxmd.com/read/29737353/induction-of-necrotic-cell-death-and-activation-of-sting-in-the-tumor-microenvironment-via-cationic-silica-nanoparticles-leading-to-enhanced-antitumor-immunity
#3
Myunggi An, Chunsong Yu, Jingchao Xi, Joyce Reyes, Guangzhao Mao, Wei-Zen Wei, Haipeng Liu
Nanotechnology has demonstrated tremendous clinical utility, with potential applications in cancer immunotherapy. Although nanoparticles with intrinsic cytotoxicity are often considered unsuitable for clinical applications, such toxicity may be harnessed in the fight against cancer. Nanoparticle-associated toxicity can induce acute necrotic cell death, releasing tumor-associated antigens which may be captured by antigen-presenting cells to initiate or amplify tumor immunity. To test this hypothesis, cytotoxic cationic silica nanoparticles (CSiNPs) were directly administered into B16F10 melanoma implanted in C57BL/6 mice...
May 8, 2018: Nanoscale
https://www.readbyqxmd.com/read/29702142/dual-tlr-agonist-nanodiscs-as-a-strong-adjuvant-system-for-vaccines-and-immunotherapy
#4
Rui Kuai, Xiaoqi Sun, Wenmin Yuan, Lukasz J Ochyl, Yao Xu, Alireza Hassani Najafabadi, Lindsay Scheetz, Min-Zhi Yu, Ishina Balwani, Anna Schwendeman, James J Moon
Recent studies have shown that certain combinations of Toll-like receptor (TLR) agonists can induce synergistic immune activation. However, it remains challenging to achieve such robust responses in vivo in a manner that is effective, facile, and amenable for clinical translation. Here, we show that MPLA, a TLR4 agonist, and CpG, a TLR9 agonist, can be efficiently co-loaded into synthetic high-density lipoprotein nanodiscs, forming a potent adjuvant system (ND-MPLA/CpG) that can be readily combined with a variety of subunit antigens, including proteins and peptides...
April 24, 2018: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/29670880/targeting-tumor-associated-macrophages-as-a-potential-strategy-to-enhance-the-response-to-immune-checkpoint-inhibitors
#5
REVIEW
Luca Cassetta, Takanori Kitamura
Inhibition of immune checkpoint pathways in CD8+ T cell is a promising therapeutic strategy for the treatment of solid tumors that has shown significant anti-tumor effects and is now approved by the FDA to treat patients with melanoma and lung cancer. However the response to this therapy is limited to a certain fraction of patients and tumor types, for reasons still unknown. To ensure success of this treatment, CD8+ T cells, the main target of the checkpoint inhibitors, should exert full cytotoxicity against tumor cells...
2018: Frontiers in Cell and Developmental Biology
https://www.readbyqxmd.com/read/29669928/cx3cr1-identifies-pd-1-therapy-responsive-cd8-t-cells-that-withstand-chemotherapy-during-cancer-chemoimmunotherapy
#6
Yiyi Yan, Siyu Cao, Xin Liu, Susan M Harrington, Wendy E Bindeman, Alex A Adjei, Jin Sung Jang, Jin Jen, Ying Li, Pritha Chanana, Aaron S Mansfield, Sean S Park, Svetomir N Markovic, Roxana S Dronca, Haidong Dong
Although immune checkpoint inhibitors have resulted in durable clinical benefits in a subset of patients with advanced cancer, some patients who did not respond to initial anti-PD-1 therapy have been found to benefit from the addition of salvage chemotherapy. However, the mechanism responsible for the successful chemoimmunotherapy is not completely understood. Here we show that a subset of circulating CD8+ T cells expressing the chemokine receptor CX3CR1 are able to withstand the toxicity of chemotherapy and are increased in patients with metastatic melanoma who responded to chemoimmunotherapy (paclitaxel and carboplatin plus PD-1 blockade)...
April 19, 2018: JCI Insight
https://www.readbyqxmd.com/read/29656492/pd-1-blockade-cellular-vesicles-for-cancer-immunotherapy
#7
Xudong Zhang, Chao Wang, Jinqiang Wang, Quanyin Hu, Benjamin Langworthy, Yanqi Ye, Wujin Sun, Jing Lin, Tianfu Wang, Jason Fine, Hao Cheng, Gianpietro Dotti, Peng Huang, Zhen Gu
Cancer cells resist to the host immune antitumor response via multiple suppressive mechanisms, including the overexpression of PD-L1 that exhausts antigen-specific CD8+ T cells through PD-1 receptors. Checkpoint blockade antibodies against PD-1 or PD-L1 have shown unprecedented clinical responses. However, limited host response rate underlines the need to develop alternative engineering approaches. Here, engineered cellular nanovesicles (NVs) presenting PD-1 receptors on their membranes, which enhance antitumor responses by disrupting the PD-1/PD-L1 immune inhibitory axis, are reported...
April 14, 2018: Advanced Materials
https://www.readbyqxmd.com/read/29627136/teipp-antigens-for-t-cell-based-immunotherapy-of-immune-edited-hla-class-i-low-cancers
#8
Koen A Marijt, Elien M Doorduijn, Thorbald van Hall
T-cell based immunotherapies through checkpoint blockade or adoptive transfer are effective treatments for a wide range of cancers like melanomas and lung carcinomas that harbor a high mutational load. The HLA class I and class II (HLA-I and HLA-II) presented neoantigens arise from genetic mutations in the cancerous cells and are ideal non-self targets for the T cell-based treatments. Although some cancer patients responded with complete regression, many others are irresponsive to checkpoint blockade treatments, or relapse after initial success...
April 4, 2018: Molecular Immunology
https://www.readbyqxmd.com/read/29619980/targeting-myeloid-derived-suppressor-cells-and-programmed-death-ligand-1-confers-therapeutic-advantage-of-ablative-hypofractionated-radiation-therapy-compared-with-conventional-fractionated-radiation-therapy
#9
Jie Lan, Rui Li, Li-Mei Yin, Lei Deng, Jun Gui, Bao-Qing Chen, Lin Zhou, Mao-Bin Meng, Qiao-Rong Huang, Xian-Ming Mo, Yu-Quan Wei, Bo Lu, Adam Dicker, Jian-Xin Xue, You Lu
PURPOSE: Ablative hypofractionated radiation therapy (AHFRT) presents a therapeutic advantage compared with conventional fractionated radiation therapy (CFRT) for primary and oligometastatic cancers. However, the underlying mechanisms remain largely unknown. In the present study, we compared the immune alterations in response to AHFRT versus CFRT and examined the significance of immune regulations contributing to the efficacy of AHFRT. METHODS AND MATERIALS: We established subcutaneous tumors using syngeneic lung cancer and melanoma cells in both immunocompetent and immunocompromised mice and treated them with AHFRT and CFRT under the same biologically equivalent dose...
May 1, 2018: International Journal of Radiation Oncology, Biology, Physics
https://www.readbyqxmd.com/read/29617862/generation-of-tumor-antigen-specific-murine-cd8-t-cells-with-enhanced-anti-tumor-activity-via-highly-efficient-crispr-cas9-genome-editing
#10
Yasuo Ouchi, Ashwini Patil, Yusuke Tamura, Hiroshi Nishimasu, Aina Negishi, Sudip Kumar Paul, Naoki Takemura, Takeshi Satoh, Yasumasa Kimura, Makoto Kurachi, Osamu Nureki, Kenta Nakai, Hiroshi Kiyono, Satoshi Uematsu
Immunotherapies have led to the successful development of novel therapies for cancer. However, there is increasing concern regarding the adverse effects caused by non-tumor-specific immune responses. Here, we report an effective strategy to generate high-avidity tumor-antigen-specific CTLs, using Cas9/single-guide RNA (sgRNA) ribonucleoprotein (RNP) delivery. As a proof-of-principle demonstration, we selected the gp100 melanoma-associated tumor antigen, and cloned the gp100-specific high-avidity TCR from gp100-immunized mice...
April 3, 2018: International Immunology
https://www.readbyqxmd.com/read/29600445/tumor-lysate-based-vaccines-on-the-road-to-immunotherapy-for-gallbladder-cancer
#11
REVIEW
Daniel Rojas-Sepúlveda, Andrés Tittarelli, María Alejandra Gleisner, Ignacio Ávalos, Cristián Pereda, Iván Gallegos, Fermín Eduardo González, Mercedes Natalia López, Jean Michel Butte, Juan Carlos Roa, Paula Fluxá, Flavio Salazar-Onfray
Immunotherapy based on checkpoint blockers has proven survival benefits in patients with melanoma and other malignancies. Nevertheless, a significant proportion of treated patients remains refractory, suggesting that in combination with active immunizations, such as cancer vaccines, they could be helpful to improve response rates. During the last decade, we have used dendritic cell (DC) based vaccines where DCs loaded with an allogeneic heat-conditioned melanoma cell lysate were tested in a series of clinical trials...
March 29, 2018: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/29599411/cd103-tumor-resident-cd8-t-cells-are-associated-with-improved-survival-in-immunotherapy-na%C3%A3-ve-melanoma-patients-and-expand-significantly-during-anti-pd-1-treatment
#12
Jarem Edwards, James S Wilmott, Jason Madore, Tuba Nur Gide, Camelia Quek, Annie Tasker, Angela Ferguson, Jinbiao Chen, Rehana Hewavisenti, Peter Hersey, Thomas Gebhardt, Wolfgang Weninger, Warwick J Britton, Robyn P M Saw, John F Thompson, Alexander M Menzies, Georgina V Long, Richard A Scolyer, Umaimainthan Palendira
Purpose: Therapeutic blockade of immune checkpoints has revolutionized cancer treatment. Durable responses, however, occur in less than half of those treated, and efforts to improve treatment efficacy are confounded by a lack of understanding of the characteristics of the cells that initiate antitumor immune response. Experimental Design: We performed multiparameter flow cytometry and quantitative multiplex immunofluorescence staining on tumor specimens from immunotherapy-naïve melanoma patients and longitudinal biopsy specimen obtained from patients undergoing anti-PD-1 therapy...
March 29, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29568696/aplastic-anemia-secondary-to-nivolumab-and-ipilimumab-in-a-patient-with-metastatic-melanoma-a-case-report
#13
D E Meyers, W F Hill, A Suo, V Jimenez-Zepeda, T Cheng, N A Nixon
Background: Immune checkpoint blockade (ICB) is becoming an increasingly prevalent strategy in the clinical realm of cancer therapeutics. With more patients being administered ICB for a host of tumor types, the scope of adverse events associated with these drugs will likely grow. Here we report a case of aplastic anemia (AA) in a patient with metastatic melanoma secondary to dual ICB therapy. To our knowledge, this is only the second case of AA secondary to dual ICB in the literature, and the first to have a positive patient outcome...
2018: Experimental Hematology & Oncology
https://www.readbyqxmd.com/read/29556352/the-enhanced-antitumor-specific-immune-response-with-mannose-and-cpg-odn-coated-liposomes-delivering-trp2-peptide
#14
Chunhui Lai, Siliang Duan, Fang Ye, Xiaoqiong Hou, Xi Li, Jin Zhao, Xia Yu, Zixi Hu, Zhuoran Tang, Fengzhen Mo, Xiaomei Yang, Xiaoling Lu
PURPOSE: Dendritic cell (DC)-based cancer vaccines is a newly emerging and potent form of immune therapy. As for any new technology, there are still considerable challenges that need to be addressed. Here, we investigate the antitumor potential of a novel liposomal vaccine, M/CpG-ODN-TRP2-Lipo. METHODS: We developed a vaccination strategy by assembling the DC-targeting mannose and immune adjuvant CpG-ODN on the surface of liposomes, which were loaded with melanoma-specific TRP2180-188 peptide as liposomal vaccine...
2018: Theranostics
https://www.readbyqxmd.com/read/29540489/survivin-monoclonal-antibodies-detect-survivin-cell-surface-expression-and-inhibit-tumor-growth-in-vivo
#15
Robert A Fenstermaker, Sheila A Figel, Jingxin Qiu, Tara A Barone, Sanam S Dharma, Evan K Winograd, Phillip M Galbo, Laura M Wiltsie, Michael J Ciesielski
Purpose: Survivin is an inhibitor of apoptosis protein (IAP) that is highly expressed in many cancers and represents an attractive molecule for targeted cancer therapy. Although primarily regarded as an intracellular protein with diverse actions, survivin has also been identified in association with circulating tumor exosomes. Experimental Design: We have reported that active, specific vaccination with a long peptide survivin immunogen leads to the development of survivin-specific CD8-mediated tumor cell lysis and prolongation of survival in tumor-bearing mice...
March 14, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29535720/t-cell-specific-loss-of-the-pi-3-kinase-p110%C3%AE-catalytic-subunit-results-in-enhanced-cytokine-production-and-antitumor-response
#16
Laura Aragoneses-Fenoll, Gloria Ojeda, María Montes-Casado, Yeny Acosta-Ampudia, Umberto Dianzani, Pilar Portolés, José M Rojo
Class IA phosphatidylinositol 3-kinase (PI3K) catalytic subunits p110α and p110δ are targets in cancer therapy expressed at high levels in T lymphocytes. The role of p110δ PI3K in normal or pathological immune responses is well established, yet the importance of p110α subunits in T cell-dependent immune responses is not clear. To address this problem, mice with p110α conditionally deleted in CD4+ and CD8+ T lymphocytes (p110α-/- ΔT) were used. p110α-/- ΔT mice show normal development of T cell subsets, but slightly reduced numbers of CD4+ T cells in the spleen...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29515971/the-expression-and-prognostic-impact-of-immune-cytolytic-activity-related-markers-in-human-malignancies-a-comprehensive-meta-analysis
#17
Constantinos Roufas, Dimitrios Chasiotis, Anestis Makris, Christodoulos Efstathiades, Christos Dimopoulos, Apostolos Zaravinos
Background: Recently, immune-checkpoint blockade has shown striking clinical results in different cancer patients. However, a significant inter-individual and inter-tumor variability exists among different cancers. The expression of the toxins granzyme A (GZMA) and perforin 1 (PRF1), secreted by effector cytotoxic T cells and natural killer (NK) cells, were recently used as a denominator of the intratumoral immune cytolytic activity (CYT). These levels are significantly elevated upon CD8+ T-cell activation as well as during a productive clinical response against immune-checkpoint blockade therapies...
2018: Frontiers in Oncology
https://www.readbyqxmd.com/read/29512369/myeloid-derived-suppressor-cells-elimination-by-5-fluorouracil-increased-dendritic-cell-based-vaccine-function-and-improved-immunity-in-tumor-mice
#18
Najmeh Khosravianfar, Jamshid Hadjati, Afshin Namdar, Roobina Boghozian, Morteza Hafezi, Mahboubeh Ashourpour, Nasim Kheshtchin, Mahsa Banitalebi, Reza Mirzaei, Seyed Alireza Razavi
Myeloid-derived suppressor cells (MDSCs) are capable of suppressing the immune response. 5-Fluorouracil (5-FU) compared to other chemotherapy drugs have shown considerable decreases in the number of MDSCs without visible effects on T, B and natural killer cells, as well as dendritic cells (DCs). DC-based vaccines considered to be appropriate candidates for cancer immunotherapy. However, due to the presence of various factors like MDSCs in tumor microenvironment, DC vaccine cannot effectively perform its function...
February 2018: Iranian Journal of Allergy, Asthma, and Immunology
https://www.readbyqxmd.com/read/29499438/necroptotic-cancer-cells-mimicry-nanovaccine-boosts-anti-tumor-immunity-with-tailored-immune-stimulatory-modality
#19
Ting Kang, Yukun Huang, Qianqian Zhu, Hao Cheng, Yuanyuan Pei, Jingxian Feng, Minjun Xu, Gan Jiang, Qingxiang Song, Tianze Jiang, Hongzhuan Chen, Xiaoling Gao, Jun Chen
Recent breakthroughs in cancer immunotherapy offer new paradigm-shifting therapeutic options for combating cancer. Personalized therapeutic anti-cancer vaccines training T cells to directly fight against tumor cells endogenously offer tremendous benefits in working synergistically with immune checkpoint inhibitors. Biomimetic nanotechnology offers a versatile platform to boost anticancer immunity by efficiently co-delivering optimized immunogenic antigen materials and adjuvants to antigen presenting cells (APC)...
May 2018: Biomaterials
https://www.readbyqxmd.com/read/29485973/self-adjuvanting-nanoemulsion-targeting-dendritic-cell-receptor-clec9a-enables-antigen-specific-immunotherapy
#20
Bijun Zeng, Anton Pj Middelberg, Adrian Gemiarto, Kelli MacDonald, Alan G Baxter, Meghna Talekar, Davide Moi, Kirsteen M Tullett, Irina Caminschi, Mireille H Lahoud, Roberta Mazzieri, Riccardo Dolcetti, Ranjeny Thomas
Non-antigen-specific stimulatory cancer immunotherapies are commonly complicated by off-target effects. Antigen-specific immunotherapy, combining viral tumor antigen or personalized neoepitopes with immune targeting, offers a solution. However, the lack of flexible systems targeting tumor antigens to cross-presenting dendritic cells (DCs) limits clinical development. Although antigen-anti-Clec9A mAb conjugates target cross-presenting DCs, adjuvant must be codelivered for cytotoxic T lymphocyte (CTL) induction...
May 1, 2018: Journal of Clinical Investigation
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