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CD8 cancer tumor melanoma

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https://www.readbyqxmd.com/read/28944501/synergistic-effects-of-interferon-beta-and-nivolumab-in-oral-mucosal-melanoma
#1
Takayuki Fusumae, Koji Kamiya, Binluen Chiang, Hirofumi Okada, Naomi Nakano, Takeo Maekawa, Mayumi Komine, Satoru Murata, Mamitaro Ohtsuki
Mucosal melanoma is a rare aggressive cancer with a very poor prognosis. Clinical and pathological characteristics of mucosal melanoma differ from those of cutaneous melanoma and there are no established management guidelines for mucosal melanoma. Complete surgical excision is one of the most effective treatments for localized lesions, while targeted therapies and immunotherapies, such as monoclonal antibodies that target cytotoxic T-lymphocyte-associated molecule-4, and the programmed death (PD)-1/PD-ligand 1 pathway inhibitors, are treatment options for unresectable or metastatic lesions...
September 25, 2017: Journal of Dermatology
https://www.readbyqxmd.com/read/28938530/cd3xpdl1-bi-specific-t-cell-engager-bite-simultaneously-activates-t-cells-and-nkt-cells-kills-pdl1-tumor-cells-and-extends-the-survival-of-tumor-bearing-humanized-mice
#2
Lucas A Horn, Nicholas G Ciavattone, Ryan Atkinson, Netsanet Woldergerima, Julia Wolf, Virginia K Clements, Pratima Sinha, Munanchu Poudel, Suzanne Ostrand-Rosenberg
Bi-specific T cell engagers (BiTEs) activate T cells through CD3 and target activated T cells to tumor-expressed antigens. BiTEs have shown therapeutic efficacy in patients with liquid tumors; however, they do not benefit all patients. Anti-tumor immunity is limited by Programmed Death 1 (PD1) pathway-mediated immune suppression, and patients who do not benefit from existing BiTES may be non-responders because their T cells are anergized via the PD1 pathway. We have designed a BiTE that activates and targets both T cells and NKT cells to PDL1(+) cells...
August 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28932640/co-delivery-of-the-nkt-agonist-%C3%AE-galactosylceramide-and-tumor-antigens-to-cross-priming-dendritic-cells-breaks-tolerance-to-self-antigens-and-promotes-antitumor-responses
#3
Reem Ghinnagow, Julie De Meester, Luis Javier Cruz, Caroline Aspord, Stéphanie Corgnac, Elodie Macho-Fernandez, Daphnée Soulard, Josette Fontaine, Laurence Chaperot, Julie Charles, Fabrice Soncin, Fathia Mami-Chouaib, Joel Plumas, Christelle Faveeuw, François Trottein
Vaccines designed to abrogate the tolerance of tumor self-antigens and amplify cytotoxic CD8(+) T cells (CTLs) have promise for the treatment of cancer. Type I natural killer (NKT) cells have attracted considerable interest in the cancer therapy field. In the current study, we have exploited the unique ability of NKT cells to serve as T-helper cells to license dendritic cells (DCs) for cross priming with the aim to generate efficient CTL antitumor responses. To this end, we designed a nanoparticle-based vaccine to target cross-priming DCs via the Clec9a endocytic pathway...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28920003/cd226-natural-killer-cells-fail-to-establish-stable-contacts-with-cancer-cells-and-show-impaired-control-of-tumor-metastasis-in-vivo
#4
Ji Sung Kim, Bo Ram Shin, Hong Kyung Lee, Jae Hee Lee, Ki Hun Kim, Jeong Eun Choi, A Young Ji, Jin Tae Hong, Youngsoo Kim, Sang-Bae Han
CD226 is an activating receptor expressed on natural killer (NK) cells, CD8(+) T cells, and other immune cells. Upon binding to its ligands expressed on target cells, CD226 activates intracellular signaling that triggers cytokine production and degranulation in NK cells. However, the role of CD226 in contact dynamics between NK and cancer cells has remained unclear. Our time-lapse images showed that individual wild-type CD226(+) NK cells contacted B16F10 melanoma cells for 23.7 min, but Cd226(-/-) NK cells only for 12...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28919783/toll-like-receptors-7-and-8-expression-correlates-with-the-expression-of-immune-biomarkers-and-positively-predicts-the-clinical-outcome-of-patients-with-melanoma
#5
Moucheng Zhang, Zhilong Yan, Junjiang Wang, Xueqing Yao
BACKGROUND: Toll-like receptors (TLRs) play a critical role in cancer, yet the clinical relevance of TLR7/8 expression in melanoma remains unclear. This study aimed to evaluate the prognostic value of TLR7/8 mRNA levels in melanoma and their correlation with immune biomarkers relevant to disease progression. METHODS: Normalized gene expression and corresponding clinical data of patients with skin cutaneous melanoma were obtained from two public databases: the Cancer Genome Atlas and GSE19234...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/28918288/th9-cells-promote-antitumor-immunity-via-il-9-and-il-21-and-demonstrate-atypical-cytokine-expression-in-breast-cancer
#6
Fa-Ping You, Jian Zhang, Tao Cui, Rui Zhu, Chong-Qing Lv, Hai-Tao Tang, Di-Wen Sun
Breast cancer is a major cause of cancer-related death in women. Antitumor T cell responses play critical therapeutic roles, including direct cytotoxicity mediated by CD8(+) T cells and immunomodulatory roles mediated by CD4(+) T cells. The IL-9-expressing Th9 cells are recently found to present antitumor immunity in melanoma and lung adenocarcinoma. In this study, we found that IL-9 expression in the serum and in circulating CD4(+) T cells were significantly upregulated in breast cancer patients compared to healthy controls...
September 14, 2017: International Immunopharmacology
https://www.readbyqxmd.com/read/28884480/blood-monocytes-sample-melana-mart1-antigen-for-long-lasting-cross-presentation-to-cd8-t-cells-after-differentiation-into-dendritic-cells
#7
Florence Faure, Mabel Jouve, Isabelle Lebhar-Peguillet, Charlotte Sadaka, Fernando Sepulveda, Olivier Lantz, Stefano Berre, Raphael Gaudin, Silvia Sánchez-Ramón, Sebastian Amigorena
Human blood monocytes are very potent to take up antigens. Like macrophages in tissue, they efficiently degrade exogenous protein and are less efficient than dendritic cells at cross-presenting antigens to CD8(+) T cells. Although it is generally accepted that dendritic cells take up tissue antigens and then migrate to lymph nodes to prime T cells, the mechanisms of presentation of antigens taken up by monocytes are poorly documented so far. In the present work, we show that monocytes loaded in vitro with MelanA long peptides retain the capacity to stimulate antigen-specific CD8(+) T cell clones after 5 days of differentiation into monocytes-derived dendritic cells (MoDC)...
September 7, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/28863272/recombinant-protein-rmbp-nap-restricts-tumor-progression-by-triggering-antitumor-immunity-in-mouse-metastatic-lung-cancer
#8
Ting Wang, Mingxuan Du, Zhenyu Ji, Cong Ding, Chengbo Wang, Yingli Men, Shimeng Liu, Taotao Liang, Xin Liu, Qiaozhen Kang
Recombinant Helicobacter pylori neutrophil-activating protein fused with Maltose- binding protein (rMBP-NAP), a potential TLR2 ligand, was reported to possess immunomodulatory effects on in-situ tumor in our previous study. In present work, we attempt to elucidate the effect of rMBP-NAP at the local immune modulation in B16-F10-induced metastatic lung cancer. Our results demonstrated that growth of B16-F10 melanoma metastases in the lung was significantly arrested after rMBP-NAP treatment, along with marked reduction in metastatic lung nodules and significant increase in survival...
September 1, 2017: Canadian Journal of Physiology and Pharmacology
https://www.readbyqxmd.com/read/28861327/a-human-recombinant-il-7-hgf%C3%AE-hybrid-cytokine-enhances-antitumor-immunity-in-mice
#9
Feng Han, Rong Hu, Min Su, Yanni Yu, Hua Yang, Laijun Lai
We purified a hybrid cytokine that contains interleukin-7 (IL-7) and the beta-chain of hepatocyte growth factor (HGFβ) from a unique long-term murine bone marrow culture system. We have cloned and expressed the human form of IL-7/HGFβ in which the IL-7 and HGFβ genes are connected by a flexible linker to produce a single-chain recombinant human IL-7/HGFβ protein (hrIL-7/HGFβ). To determine whether hrIL-7/HGFβ has antitumor activity, we injected this hybrid cytokine into melanoma and colon cancer animal models, and then assessed the local tumor growth and tumor metastasis...
2017: American Journal of Cancer Research
https://www.readbyqxmd.com/read/28858473/molecular-targeted-immunotherapeutic-strategy-for-melanoma-via-dual-targeting-nanoparticles-delivering-small-interfering-rna-to-tumor-associated-macrophages
#10
Yuan Qian, Sha Qiao, Yanfeng Dai, Guoqiang Xu, Bolei Dai, Lisen Lu, Xiang Yu, Qingming Luo, Zhihong Zhang
Tumor-associated macrophages (TAMs) are a promising therapeutic target for cancer immunotherapy. Targeted delivery of therapeutic drugs to the tumor-promoting M2-like TAMs is challenging. Here, we developed M2-like TAM dual-targeting nanoparticles (M2NPs), whose structure and function were controlled by α-peptide (a scavenger receptor B type 1 (SR-B1) targeting peptide) linked with M2pep (an M2 macrophage binding peptide). By loading anti-colony stimulating factor-1 receptor (anti-CSF-1R) small interfering RNA (siRNA) on the M2NPs, we developed a molecular-targeted immunotherapeutic approach to specifically block the survival signal of M2-like TAMs and deplete them from melanoma tumors...
September 6, 2017: ACS Nano
https://www.readbyqxmd.com/read/28814733/enhancing-immune-responses-to-cancer-vaccines-using-multi-site-injections
#11
Robert C Mould, Amanda W K AuYeung, Jacob P van Vloten, Leonardo Susta, Anthony J Mutsaers, James J Petrik, Geoffrey A Wood, Sarah K Wootton, Khalil Karimi, Byram W Bridle
For a vaccine to be effective it must induce a sufficiently robust and specific immune response. Multi-site injection protocols can increase the titers of rabies virus-neutralizing antibodies. Hypothetically, spreading a vaccine dose across multiple lymphatic drainage regions could also potentiate T cell responses. We used a replication-deficient adenovirus serotype 5-vectored cancer vaccine targeting the melanoma-associated antigen dopachrome tautomerase. Clinically, high numbers of tumor-infiltrating CD8(+) T cells are a positive prognostic indicator...
August 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28811960/rehmannia-glutinosa-polysaccharide-induces-toll-like-receptor-4-dependent-spleen-dendritic-cell-maturation-and-anti-cancer-immunity
#12
Li Xu, Minseok Kwak, Wei Zhang, Ling Zeng, Peter Chang-Whan Lee, Jun-O Jin
Rehmannia glutinosa polysaccharide (RGP) has shown an activation of immune cells in vitro. However, the immune stimulatory effect of RGP in a mouse in vivo is not well studied. In this study, we examined the effect of RGP on dendritic cell (DC) activation and anticancer immunity in vivo. Treatments of RGP in C56BL/6 mice induced increased levels of co-stimulatory molecule expression and pro-inflammatory cytokine production in spleen DCs dependent on toll-like receptor 4 (TLR4), and those DCs promoted interferon-gamma (IFNγ) production in CD4(+) and CD8(+) T cells...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28776578/negative-immune-checkpoint-regulation-by-vista-a-mechanism-of-acquired-resistance-to-anti-pd-1-therapy-in-metastatic-melanoma-patients
#13
Hojabr Kakavand, Louise A Jackett, Alexander M Menzies, Tuba N Gide, Matteo S Carlino, Robyn P M Saw, John F Thompson, James S Wilmott, Georgina V Long, Richard A Scolyer
Understanding the mechanisms of acquired resistance to anti-PD-1 will allow development of better treatment strategies for cancer patients. This study evaluated potential mechanisms of acquired resistance to anti-PD-1 in longitudinally collected metastatic melanoma patient biopsies. Thirty-four metastatic melanoma biopsies were collected from 16 patients who had initially responded to either anti-PD-1 (n=13) alone or combination of anti-PD-1 and ipilimumab (n=3) and then progressed. Biopsies were taken prior to treatment (PRE, n=12) and following progression of disease (PROG, n=22)...
August 4, 2017: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
https://www.readbyqxmd.com/read/28770166/genomic-signature-of-the-natural-oncolytic-herpes-simplex-virus-hf10-and-its-therapeutic-role-in-preclinical-and-clinical-trials
#14
REVIEW
Ibrahim Ragab Eissa, Yoshinori Naoe, Itzel Bustos-Villalobos, Toru Ichinose, Maki Tanaka, Wu Zhiwen, Nobuaki Mukoyama, Taishi Morimoto, Noriyuki Miyajima, Hasegawa Hitoki, Seiji Sumigama, Branko Aleksic, Yasuhiro Kodera, Hideki Kasuya
Oncolytic viruses (OVs) are opening new possibilities in cancer therapy with their unique mechanism of selective replication within tumor cells and triggering of antitumor immune responses. HF10 is an oncolytic herpes simplex virus-1 with a unique genomic structure that has non-engineered deletions and insertions accompanied by frame-shift mutations, in contrast to the majority of engineered OVs. At the genetic level, HF10 naturally lacks the expression of UL43, UL49.5, UL55, UL56, and latency-associated transcripts, and overexpresses UL53 and UL54...
2017: Frontiers in Oncology
https://www.readbyqxmd.com/read/28765120/constitutive-ido1-expression-in-human-tumors-is-driven-by-cyclooxygenase-2-and-mediates-intrinsic-immune-resistance
#15
Marc Hennequart, Luc Pilotte, Stefania Cane, Delia Hoffmann, Vincent Stroobant, Etienne De Plaen, Benoît J Van den Eynde
Tumors use various mechanisms to avoid immune destruction. Cyclooxygenase-2 (COX-2) expression may be a driver of immune suppression in melanoma, but the mechanisms involved remain elusive. Here, we show that COX-2 expression drives constitutive expression of indoleamine 2,3-dioxygenase 1 (IDO1) in human tumor cells. IDO1 is an immunosuppressive enzyme that degrades tryptophan. In a series of seven human tumor lines, constitutive IDO1 expression depends on COX-2 and prostaglandin E2 (PGE2), which, upon autocrine signaling through the EP receptor, activates IDO1 via the PKC and PI3K pathways...
August 2017: Cancer Immunology Research
https://www.readbyqxmd.com/read/28763794/targeting-latency-associated-peptide-promotes-antitumor-immunity
#16
Galina Gabriely, Andre P da Cunha, Rafael M Rezende, Brendan Kenyon, Asaf Madi, Tyler Vandeventer, Nathaniel Skillin, Stephen Rubino, Lucien Garo, Maria A Mazzola, Panagiota Kolypetri, Amanda J Lanser, Thais Moreira, Ana Maria C Faria, Hans Lassmann, Vijay Kuchroo, Gopal Murugaiyan, Howard L Weiner
Regulatory T cells (Tregs) promote cancer by suppressing antitumor immune responses. We found that anti-LAP antibody, which targets the latency-associated peptide (LAP)/transforming growth factor-β (TGF-β) complex on Tregs and other cells, enhances antitumor immune responses and reduces tumor growth in models of melanoma, colorectal carcinoma, and glioblastoma. Anti-LAP decreases LAP(+) Tregs, tolerogenic dendritic cells, and TGF-β secretion and is associated with CD8(+) T cell activation. Anti-LAP increases infiltration of tumors by cytotoxic CD8(+) T cells and reduces CD103(+) CD8 T cells in draining lymph nodes and the spleen...
May 19, 2017: Science Immunology
https://www.readbyqxmd.com/read/28763790/platelets-subvert-t-cell-immunity-against-cancer-via-garp-tgf%C3%AE-axis
#17
Saleh Rachidi, Alessandra Metelli, Brian Riesenberg, Bill X Wu, Michelle H Nelson, Caroline Wallace, Chrystal M Paulos, Mark P Rubinstein, Elizabeth Garrett-Mayer, Mirko Hennig, Daniel W Bearden, Yi Yang, Bei Liu, Zihai Li
Cancer-associated thrombocytosis has long been linked to poor clinical outcome, but the underlying mechanism is enigmatic. We hypothesized that platelets promote malignancy and resistance to therapy by dampening host immunity. We show that genetic targeting of platelets enhances adoptive T cell therapy of cancer. An unbiased biochemical and structural biology approach established transforming growth factor β (TGFβ) and lactate as major platelet-derived soluble factors to obliterate CD4(+) and CD8(+) T cell functions...
May 5, 2017: Science Immunology
https://www.readbyqxmd.com/read/28751442/towards-precision-radiotherapy-for-use-with-immune-checkpoint-blockers
#18
Claire Vanpouille-Box, Silvia C Formenti, Sandra Demaria
The first evidence that radiation therapy (RT) enhances the efficacy of immune checkpoint blockers (ICBs) was obtained a dozen years ago in a mouse model of metastatic carcinoma refractory to anti-CTLA-4 treatment. At the time, ICBs had just entered clinical testing, an endeavor that culminated in 2011 with the approval of the first anti-CTLA-4 antibody for use in metastatic melanoma patients (ipilimumab). Thereafter, some patients progressing on ipilimumab showed systemic responses only upon receiving radiation to one lesion, confirming clinically the pro-immunogenic effects of radiation...
July 27, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28746871/the-histone-methyltransferase-ezh2-controls-mechanisms-of-adaptive-resistance-to-tumor-immunotherapy
#19
Daniel Zingg, Natalia Arenas-Ramirez, Dilara Sahin, Rodney A Rosalia, Ana T Antunes, Jessica Haeusel, Lukas Sommer, Onur Boyman
Immunotherapy and particularly immune checkpoint inhibitors have resulted in remarkable clinical responses in patients with immunogenic tumors, although most cancers develop resistance to immunotherapy. The molecular mechanisms of tumor resistance to immunotherapy remain poorly understood. We now show that induction of the histone methyltransferase Ezh2 controls several tumor cell-intrinsic and extrinsic resistance mechanisms. Notably, T cell infiltration selectively correlated with high EZH2-PRC2 complex activity in human skin cutaneous melanoma...
July 25, 2017: Cell Reports
https://www.readbyqxmd.com/read/28733349/constitutive-ido1-expression-in-human-tumors-is-driven-by-cyclooxygenase-2-and-mediates-intrinsic-immune-resistance
#20
Marc Hennequart, Luc Pilotte, Stefania Cane, Delia Hoffmann, Vincent Stroobant, Etienne De Plaen, Benoît J Van den Eynde
Tumors use various mechanisms to avoid immune destruction. Cyclooxygenase-2 (COX-2) expression may be a driver of immune suppression in melanoma, but the mechanisms involved remain elusive. Here, we show that COX-2 expression drives constitutive expression of indoleamine 2,3-dioxygenase 1 (IDO1) in human tumor cells. IDO1 is an immunosuppressive enzyme that degrades tryptophan. In a series of seven human tumor lines, constitutive IDO1 expression depends on COX-2 and prostaglandin E2 (PGE2), which, upon autocrine signaling through the EP receptor, activates IDO1 via the PKC and PI3K pathways...
July 21, 2017: Cancer Immunology Research
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