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Melanoma antigene gene

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https://www.readbyqxmd.com/read/27918555/gene-expression-profiling-of-anti-ctla4-treated-metastatic-melanoma-in-patients-with-treatment-induced-autoimmunity
#1
Scott C Bresler, Le Min, Scott J Rodig, Andrew C Walls, Shuyun Xu, Songmei Geng, F Stephen Hodi, George F Murphy, Christine G Lian
Ipilimumab (IPI) is a monoclonal antibody that targets the inhibitory CTLA4 receptor of T cells, enhancing T-cell-driven antitumor responses. IPI therapy in metastatic melanoma results in significant improvement in disease-free and overall survival, although after initial responses disease progression generally ensues. Identification of specific responses in tissue where melanoma tumor cells are subjected to IPI-driven immune attack may reveal mechanisms of treatment efficacy or resistance, permitting refinement of targeted therapeutic approaches...
December 5, 2016: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/27910859/t-cell-programming-in-pancreatic-adenocarcinoma-a-review
#2
REVIEW
Y D Seo, V G Pillarisetty
Despite recent advancements in multimodal therapy, pancreatic ductal adenocarcinoma (PDA) continues to have a dismal prognosis. In the era of burgeoning immune therapies against previously difficult-to-treat malignancies, there has been growing interest in activating the immune system against PDA; however, unlike in other cancers such as melanoma and lymphoma, immunotherapy has not yielded many clinically significant results. To harness these mechanisms for therapeutic use, an in-depth understanding of T-cell programming in the immune microenvironment of PDA must be achieved...
December 2, 2016: Cancer Gene Therapy
https://www.readbyqxmd.com/read/27852984/characterization-of-mageg2-with-testis-specific-expression-in-mice
#3
Juri Jeong, Sora Jin, Heejin Choi, Jun Tae Kwon, Jihye Kim, Jaehwan Kim, Zee Yong Park, Chunghee Cho
Male germ cell development is a well-defined process occurring in numerous seminiferous tubules of the testis. Uncovering testicular novel genes related to intrinsic regulation of spermatogenesis is essential for the understanding of spermatogenesis. In the present study, we investigated mouse Mageg2, which belongs to a group of melanoma-associated antigens (MAGEs). Mageg2 is transcribed in the testis specifically, and its expression level is increased at the pachytene spermatocyte stage, indicating that Mageg2 is expressed predominantly in germ cells...
November 15, 2016: Asian Journal of Andrology
https://www.readbyqxmd.com/read/27843173/pilot-study-on-mage-c2-as-a-potential-biomarker-for-triple-negative-breast-cancer
#4
Qian Zhao, Wen-Ting Xu, Tuluhong Shalieer
Objective. In the current study, we measured the expression status of melanoma antigen gene c2 (MAGE-C2) in triple-negative breast cancer (TNBC) and analyzed its prognostic with the clinical pathological features of patients with TNBC. Methods. The expressions statuses of MAGE-C2 were detected in TNBC tissues and paracarcinoma tissues by immunohistochemistry, reverse transcription-polymerase chain reaction (RT-PCR), and western blotting. Then, we investigated the relationship of MAGE-C2 expression status and clinicopathological parameters of TNBC patients by the chi-squared test...
2016: Disease Markers
https://www.readbyqxmd.com/read/27837020/density-of-immunogenic-antigens-does-not-explain-the-presence-or-absence-of-the-t-cell-inflamed-tumor-microenvironment-in-melanoma
#5
Stefani Spranger, Jason J Luke, Riyue Bao, Yuanyuan Zha, Kyle M Hernandez, Yan Li, Alexander P Gajewski, Jorge Andrade, Thomas F Gajewski
Melanoma metastases can be categorized by gene expression for the presence of a T-cell-inflamed tumor microenvironment, which correlates with clinical efficacy of immunotherapies. T cells frequently recognize mutational antigens corresponding to nonsynonymous somatic mutations (NSSMs), and in some cases shared differentiation or cancer-testis antigens. Therapies are being pursued to trigger immune infiltration into non-T-cell-inflamed tumors in the hope of rendering them immunotherapy responsive. However, whether those tumors express antigens capable of T-cell recognition has not been explored...
November 29, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27819678/tet2-binds-the-androgen-receptor-and-loss-is-associated-with-prostate-cancer
#6
M L Nickerson, S Das, K M Im, S Turan, S I Berndt, H Li, H Lou, S A Brodie, J N Billaud, T Zhang, A J Bouk, D Butcher, Z Wang, L Sun, K Misner, W Tan, A Esnakula, D Esposito, W Y Huang, R N Hoover, M A Tucker, J R Keller, J Boland, K Brown, S K Anderson, L E Moore, W B Isaacs, S J Chanock, M Yeager, M Dean, T Andresson
Genetic alterations associated with prostate cancer (PCa) may be identified by sequencing metastatic tumour genomes to identify molecular markers at this lethal stage of disease. Previously, we characterized somatic alterations in metastatic tumours in the methylcytosine dioxygenase ten-eleven translocation 2 (TET2), which is altered in 5-15% of myeloid, kidney, colon and PCas. Genome-wide association studies previously identified non-coding risk variants associated with PCa and melanoma. We perform fine-mapping of PCa risk across TET2 using genotypes from the PEGASUS case-control cohort and identify six new risk variants in introns 1 and 2...
November 7, 2016: Oncogene
https://www.readbyqxmd.com/read/27779616/prime-boost-using-separate-oncolytic-viruses-in-combination-with-checkpoint-blockade-improves-anti-tumour-therapy
#7
E Ilett, T Kottke, J Thompson, K Rajani, S Zaidi, L Evgin, M Coffey, C Ralph, R Diaz, H Pandha, K Harrington, P Selby, R Bram, A Melcher, R Vile
The anti-tumour effects associated with oncolytic virus therapy are mediated significantly through immune-mediated mechanisms, which depend both on the type of virus and the route of delivery. Here, we show that intra-tumoral oncolysis by Reovirus induced the priming of a CD8+, Th1-type anti-tumour response. By contrast, systemically delivered Vesicular Stomatitis Virus expressing a cDNA library of melanoma antigens (VSV-ASMEL) promoted a potent anti-tumour CD4+ Th17 response. Therefore, we hypothesised that combining the Reovirus-induced CD8+ T cell response, with the VSV-ASMEL CD4+ Th17 helper response, would produce enhanced anti-tumour activity...
December 1, 2016: Gene Therapy
https://www.readbyqxmd.com/read/27764126/upregulation-of-hla-expression-in-primary-uveal-melanoma-by-infiltrating-leukocytes
#8
T Huibertus van Essen, Sake I van Pelt, Inge H G Bronkhorst, Mieke Versluis, Fariba Némati, Cécile Laurent, Gregorius P M Luyten, Thorbald van Hall, Peter J van den Elsen, Pieter A van der Velden, Didier Decaudin, Martine J Jager
INTRODUCTION: Uveal melanoma (UM) with an inflammatory phenotype, characterized by infiltrating leukocytes and increased human leukocyte antigen (HLA) expression, carry an increased risk of death due to metastases. These tumors should be ideal for T-cell based therapies, yet it is not clear why prognostically-infaust tumors have a high HLA expression. We set out to determine whether the level of HLA molecules in UM is associated with other genetic factors, HLA transcriptional regulators, or microenvironmental factors...
2016: PloS One
https://www.readbyqxmd.com/read/27757299/intratumoral-expression-levels-of-pd-l1-gzma-and-hla-a-along-with-oligoclonal-t-cell-expansion-associate-with-response-to-nivolumab-in-metastatic-melanoma
#9
Hiroyuki Inoue, Jae-Hyun Park, Kazuma Kiyotani, Makda Zewde, Azusa Miyashita, Masatoshi Jinnin, Yukiko Kiniwa, Ryuhei Okuyama, Ryota Tanaka, Yasuhiro Fujisawa, Hiroshi Kato, Akimichi Morita, Jun Asai, Norito Katoh, Kenji Yokota, Masashi Akiyama, Hironobu Ihn, Satoshi Fukushima, Yusuke Nakamura
Immune checkpoint inhibitors blocking the interaction between programmed death-1 (PD-1) and PD-1 ligand-1 (PD-L1) are revolutionizing the cancer immunotherapies with durable clinical responses. Although high expression of PD-L1 in tumor tissues has been implicated to correlate with the better response to the anti-PD-1 therapies, this association has been controversial. In this study, to characterize immune microenvironment in tumors, we examined mRNA levels of immune-related genes and characterized T cell repertoire in the tumors of 13 melanoma patients before and after nivolumab treatment...
2016: Oncoimmunology
https://www.readbyqxmd.com/read/27750220/blocking-tcr-restimulation-induced-necroptosis-in-adoptively-transferred-t-cells-improves-tumor-control
#10
Pravin Kesarwani, Paramita Chakraborty, Radhika Gudi, Shilpak Chatterjee, Gina Scurti, Kyle Toth, Patt Simms, Mahvash Husain, Kent Armeson, Shahid Husain, Elizabeth Garrett-Mayer, Chethamarakshan Vasu, Michael I Nishimura, Shikhar Mehrotra
Advancements in adoptive cell transfer therapy (ACT) has led to the use of T cells engineered with tumor specific T cell receptors, which after rapid expansion can be obtained in sufficient numbers for treating patients. However, due to massive proliferation these cells are close to replicative senescence, exhibit exhausted phenotype, and also display increased susceptibility to activation induced cell death. We have previously shown that tumor reactive T cells undergo caspase-independent cell death upon TCR restimulation with cognate antigen, which involves reactive oxygen species and c-jun N-terminal kinase...
October 14, 2016: Oncotarget
https://www.readbyqxmd.com/read/27716898/distinct-patterns-of-cytolytic-t-cell-activation-by-different-tumour-cells-revealed-by-ca-2-signalling-and-granule-mobilization
#11
Melissa Frick, Pierre Mouchacca, Grégory Verdeil, Yannick Hamon, Cyrille Billaudeau, Michel Buferne, Mathieu Fallet, Nathalie Auphan-Anezin, Anne-Marie Schmitt-Verhulst, Claude Boyer
Cancer-germline genes in both humans and mice have been shown to encode antigens susceptible to targeting by cytotoxic CD8 T effector cells (CTL). We analysed the ability of CTL to kill different tumour cell lines expressing the same cancer-germline gene P1A (Trap1a). We previously demonstrated that CTL expressing a T-cell receptor specific for the P1A35-43 peptide associated with H-2L(d) , although able to induce regression of P1A-expressing P815 mastocytoma cells, were much less effective against P1A-expressing melanoma cells...
October 7, 2016: Immunology
https://www.readbyqxmd.com/read/27713165/generation-of-v-%C3%AE-13-%C3%AE-21-t-cell-specific-target-cml-cells-by-tcr-gene-transfer
#12
Xianfeng Zha, Ling Xu, Shaohua Chen, Lijian Yang, Yikai Zhang, Yuhong Lu, Zhi Yu, Bo Li, Xiuli Wu, Wenjie Zheng, Yangqiu Li
Adoptive immunotherapy with antigen-specific T cells can be effective for treating melanoma and chronic myeloid leukemia (CML). However, to obtain sufficient antigen-specific T cells for treatment, the T cells have to be cultured for several weeks in vitro, but in vitro T cell expansion is difficult to control. Alternatively, the transfer of T cell receptors (TCRs) with defined antigen specificity into recipient T cells may be a simple solution for generating antigen-specific T cells. The objective of this study was to identify CML-associated, antigen-specific TCR genes and generate CML-associated, antigen-specific T cells with T cell receptor (TCR) gene transfer...
October 4, 2016: Oncotarget
https://www.readbyqxmd.com/read/27707590/development-and-validation-of-a-noninvasive-2-gene-molecular-assay-for-cutaneous-melanoma
#13
Pedram Gerami, Zuxu Yao, David Polsky, Burkhard Jansen, Klaus Busam, Jonhan Ho, Mary Martini, Laura K Ferris
BACKGROUND: Clinical and histopathologic assessment of pigmented skin lesions remains challenging even for experts. Differentiated and accurate noninvasive diagnostic modalities are highly desirable. OBJECTIVE: We sought to provide clinicians with such a tool. METHODS: A 2-gene classification method based on LINC00518 and preferentially expressed antigen in melanoma (PRAME) gene expression was evaluated and validated in 555 pigmented lesions (157 training and 398 validation samples) obtained noninvasively via adhesive patch biopsy...
October 1, 2016: Journal of the American Academy of Dermatology
https://www.readbyqxmd.com/read/27672006/p75-neurotrophin-receptor-regulates-differential-mineralization-of-rat-ectomesenchymal-stem-cells
#14
Kun Yang, Yingying Wang, Yingxin Ju, Gang Li, Chang Liu, Junyu Liu, Qi Liu, Xiujie Wen, Lu Chuan Liu
OBJECTIVES: The aim of this study was to investigate whether p75NTR (p75 neurotrophin receptor) regulates differential mineralization capacity of rEMSCs (rat ectomesenchymal stem cells) and underlying mechanisms associated with Mage-D1 (melanoma-associated antigens-D1). MATERIALS AND METHODS: Immunohistochemical staining of p75NTR in developing tooth germs was performed on E12.5d (embryonic 12.5 days) and E19.5d (embryonic 19.5 days). E12.5d EMSCs and E19.5d EMSCs were isolated in the same pregnant Sprague-Dawley rats from embryonic maxillofacial processes and tooth germs...
September 27, 2016: Cell Proliferation
https://www.readbyqxmd.com/read/27636589/establishment-of-magec2-knockout-cells-and-functional-investigation-of-magec2-in-tumor-cells
#15
Jingjing Wang, Xiao Song, Chengli Guo, Ying Wang, Yanhui Yin
MAGEC2, a cancer/testis antigen, is expressed in a wide variety of cancer types but not in normal somatic cells. MAGEC2 has long been recognized as a tumor-specific target, however, its functions remain largely unknown. In this study, we established MAGEC2-knockout A375 melanoma cell lines using the CRISPR/Cas9 system. Seven clonal cell lines were generated by using four single guide RNAs targeting the coding region of the MAGEC2 gene, which produced indels that abolished MAGEC2 protein expression. To identify the differentially expressed protein profiles associated with MAGEC2 loss, iTRAQ based comparative proteomics experiments were carried out on the MAGEC2-knockcout and control A375 cells...
September 16, 2016: Cancer Science
https://www.readbyqxmd.com/read/27625650/a-well-controlled-experimental-system-to-study-interactions-of-cytotoxic-t-lymphocytes-with-tumor-cells
#16
Natalie J Neubert, Charlotte Soneson, David Barras, Petra Baumgaertner, Donata Rimoldi, Mauro Delorenzi, Silvia A Fuertes Marraco, Daniel E Speiser
While T cell-based immunotherapies are steadily improving, there are still many patients who progress, despite T cell-infiltrated tumors. Emerging evidence suggests that T cells themselves may provoke immune escape of cancer cells. Here, we describe a well-controlled co-culture system for studying the dynamic T cell - cancer cell interplay, using human melanoma as a model. We explain starting material, controls, and culture parameters to establish reproducible and comparable cultures with highly heterogeneous tumor cells...
2016: Frontiers in Immunology
https://www.readbyqxmd.com/read/27603913/cancer-testis-antigens-expression-regulation-tumor-invasion-and-use-in-immunotherapy-of-cancers
#17
Arash Salmaninejad, Mohammad Reza Zamani, Mehrnaz Pourvahedi, Zahra Golchehre, Ali Hosseini Bereshneh, Nima Rezaei
UNLABELLED: Cancer/testis antigens (CTAs) are named based on their expression pattern that is restricted in a number of normal and abnormal tissues. Tumor cells frequently express antigens whose expression is typically restricted to germ cells. Their unique expression pattern is guaranteed by precise epigenetic regulatory mechanisms. Because of their tumor-limited, high immunogenicity, and biased expression, discovery of these molecules provides unprecedented opportunities for further research and clinical development in the field of cancer diagnosis and immunotherapy...
October 2016: Immunological Investigations
https://www.readbyqxmd.com/read/27602118/primary-splenic-b-cell-lymphoma-unclassifiable-with-features-intermediate-between-diffuse-large-b-cell-lymphoma-and-classical-hodgkin-lymphoma-a-case-report
#18
Feng Shi, Quan Zhou, Ying Gao, Xiang-Qing Cui, Hong Chang
B-cell lymphoma (BCL), unclassifiable, with features intermediate between diffuse large BCL (DLBCL) and classical Hodgkin's lymphoma (CHL), is a novel entity to the World Health Organization classification system. These tumors are rare aggressive lymphomas that have a poor prognosis. The present study reports the case of a patient with one such lymphoma that occurred in the spleen, which expressed cluster of differentiation (CD)20, CD79α, melanoma associated antigen (mutated) 1, BCL6, CD15 and CD30. Polymerase chain reaction analysis demonstrated a clonal rearrangement of the genes coding for immunoglobulin heavy chains...
September 2016: Oncology Letters
https://www.readbyqxmd.com/read/27573048/current-treatments-for-advanced-melanoma-and-introduction-of-a-promising-novel-gene-therapy-for-melanoma-review
#19
Jae-Rim Heo, Nam-Hyung Kim, Jaejin Cho, Kyung-Chul Choi
Metastatic melanoma is a fatal form of skin cancer that has a tendency to proliferate more rapidly than any other solid tumor. Since 2010, treatment options for metastatic melanoma have been developed including chemotherapies, checkpoint inhibition immunotherapies, e.g., anti‑cytotoxic T‑lymphocyte antigen‑4 (CTLA‑4) and anti‑programmed death‑1 (PD‑1), and molecular-targeted therapies, e.g., BRAF and MEK inhibitors. These treatments have shown not only high response rates yet also side‑effects and limitations...
October 2016: Oncology Reports
https://www.readbyqxmd.com/read/27549806/axl-signaling-induces-development-of-natural-killer-cells-in-vitro-and-in-vivo
#20
Eun-Mi Kim, Eun-Hee Lee, Hwa-Yeon Lee, Ha-Rim Choi, Kon-Young Ji, Su-Man Kim, Kwang Dong Kim, Hyung-Sik Kang
Natural killer (NK) cells have been well known to play a critical role in innate immunity, but they are also capable of regulating adaptive immunity through the induction of T cell-mediated memory response and B cell-mediated autoimmune response. NK cells are differentiated from hematopoietic stem cells (HSCs) in the bone marrow (BM), and a series of surface molecules are expressed on NK cells in a differentiation stage-specific manner. Axl receptor tyrosine kinase is originally identified as homeostatic regulators for antigen-presenting cells, and its ligand, growth-arrest-specific gene 6 (Gas6), has been reported to promote cell survival, proliferation, and migration, but their regulatory role in the development and effector function of NK cells is not yet fully understood...
August 22, 2016: Protoplasma
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