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Cancer neoantigens

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https://www.readbyqxmd.com/read/29027228/high-mobility-group-box-1-protein-orchestrates-responses-to-tissue-damage-via-inflammation-innate-and-adaptive-immunity-and-tissue-repair
#1
REVIEW
Marco E Bianchi, Massimo P Crippa, Angelo A Manfredi, Rosanna Mezzapelle, Patrizia Rovere Querini, Emilie Venereau
A single protein, HMGB1, directs the triggering of inflammation, innate and adaptive immune responses, and tissue healing after damage. HMGB1 is the best characterized damage-associated molecular pattern (DAMP), proteins that are normally inside the cell but are released after cell death, and allow the immune system to distinguish between antigens that are dangerous or not. Notably, cells undergoing severe stress actively secrete HMGB1 via a dedicated secretion pathway: HMGB1 is relocated from the nucleus to the cytoplasm and then to secretory lysosomes or directly to the extracellular space...
November 2017: Immunological Reviews
https://www.readbyqxmd.com/read/29022489/adar1-expression-is-associated-with-tumour-infiltrating-lymphocytes-in-triple-negative-breast-cancer
#2
In Hye Song, Young-Ae Kim, Sun-Hee Heo, In Ah Park, Miseon Lee, Won Seon Bang, Hye Seon Park, Gyungyub Gong, Hee Jin Lee
Tumours with a high mutation burden exhibit considerable neoantigens and tumour-infiltrating lymphocytes. RNA editing by ADAR1 is a source of changes in epitope. However, ADAR1 expression in cancer cells and tumour-infiltrating lymphocyte levels in triple-negative breast cancer have not been well evaluated. We immunohistochemically examined ADAR1 expression in 681 triple-negative breast cancer patients and analysed their clinicopathological characteristics. We also analysed basal-like tumours using The Cancer Genome Atlas data...
October 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28978751/an-anti-glypican-3-cd3-bispecific-t-cell-redirecting-antibody-for-treatment-of-solid-tumors
#3
Takahiro Ishiguro, Yuji Sano, Shun-Ichiro Komatsu, Mika Kamata-Sakurai, Akihisa Kaneko, Yasuko Kinoshita, Hirotake Shiraiwa, Yumiko Azuma, Toshiaki Tsunenari, Yoko Kayukawa, Yukiko Sonobe, Natsuki Ono, Kiyoaki Sakata, Toshihiko Fujii, Yoko Miyazaki, Mizuho Noguchi, Mika Endo, Asako Harada, Werner Frings, Etsuko Fujii, Eitaro Nanba, Atsushi Narita, Akihisa Sakamoto, Tetsuya Wakabayashi, Hiroko Konishi, Hiroaki Segawa, Tomoyuki Igawa, Takashi Tsushima, Hironori Mutoh, Yukari Nishito, Mina Takahashi, Lorraine Stewart, Ehab ElGabry, Yoshiki Kawabe, Masaki Ishigai, Shuichi Chiba, Masahiro Aoki, Kunihiro Hattori, Junichi Nezu
Cancer care is being revolutionized by immunotherapies such as immune checkpoint inhibitors, engineered T cell transfer, and cell vaccines. The bispecific T cell-redirecting antibody (TRAB) is one such promising immunotherapy, which can redirect T cells to tumor cells by engaging CD3 on a T cell and an antigen on a tumor cell. Because T cells can be redirected to tumor cells regardless of the specificity of T cell receptors, TRAB is considered efficacious for less immunogenic tumors lacking enough neoantigens...
October 4, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/28978689/netmhcpan-4-0-improved-peptide-mhc-class-i-interaction-predictions-integrating-eluted-ligand-and-peptide-binding-affinity-data
#4
Vanessa Jurtz, Sinu Paul, Massimo Andreatta, Paolo Marcatili, Bjoern Peters, Morten Nielsen
Cytotoxic T cells are of central importance in the immune system's response to disease. They recognize defective cells by binding to peptides presented on the cell surface by MHC class I molecules. Peptide binding to MHC molecules is the single most selective step in the Ag-presentation pathway. Therefore, in the quest for T cell epitopes, the prediction of peptide binding to MHC molecules has attracted widespread attention. In the past, predictors of peptide-MHC interactions have primarily been trained on binding affinity data...
October 4, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28977923/integrated-analysis-of-somatic-mutations-and-immune-microenvironment-of-multiple-regions-in-breast-cancers
#5
Taigo Kato, Jae-Hyun Park, Kazuma Kiyotani, Yuji Ikeda, Yasuo Miyoshi, Yusuke Nakamura
Next-generation sequencing technology enables us to analyze the complexity of intra- and inter-tumoral heterogeneity, which may influence to prognosis of cancer patients. In this study, we collected surgically-resected tumor tissues from five breast cancer patients and characterized three different portions of individual tumors through somatic mutation analysis by whole exome sequencing, T cell receptor beta (TCRB) repertoire analysis of tumor-infiltrating lymphocytes (TILs), and the expression analysis of immune-related genes at 15 different sites...
September 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28970830/immunomodulatory-monoclonal-antibodies-in-combined-immunotherapy-trials-for-cutaneous-melanoma
#6
REVIEW
Mariana Aris, José Mordoh, María Marcela Barrio
In the last few years, there has been a twist in cancer treatment toward immunotherapy thanks to the impressive results seen in advanced patients from several tumor pathologies. Cutaneous melanoma is a highly mutated and immunogenic tumor that has been a test field for the development of immunotherapy. However, there is still a way on the road to achieving complete and long-lasting responses in most patients. It is desirable that immunotherapeutic strategies induce diverse immune reactivity specific to tumor antigens, including the so-called neoantigens, as well as the blockade of immunosuppressive mechanisms...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28967094/the-inducers-of-immunogenic-cell-death-for-tumor-immunotherapy
#7
Xiuying Li
Immunotherapy is a promising treatment modality that acts by selectively harnessing the host immune defenses against cancer. An effective immune response is often needed to eliminate tumors following treatment which can trigger the immunogenicity of dying tumor cells. Some treatment modalities (such as photodynamic therapy, high hydrostatic pressure or radiotherapy) and agents (some chemotherapeutic agents, oncolytic viruses) have been used to endow tumor cells with immunogenicity and/or increase their immunogenicity...
September 18, 2017: Tumori
https://www.readbyqxmd.com/read/28945841/antigen-cross-presentation-and-t-cell-cross-priming-in-cancer-immunology-and-immunotherapy
#8
Alfonso R Sánchez-Paulete, Álvaro Teijeira, Francisco J Cueto, Saray Garasa, José L Pérez-Gracia, Álvaro Sánchez-Arráez, David Sancho, Ignacio Melero
Dendritic cells are the main professional antigen-presenting cells for induction of T cell adaptive responses. Cancer cells express tumor antigens, including neoantigens generated by non-synonymous mutations, but are poor for antigen presentation and for providing costimulatory signals for T-cell priming. Mounting evidence suggests that antigen transfer to dendritic cells (DCs) and their surrogate presentation on MHC class I and II molecules together with costimulatory signals is paramount for induction of viral and cancer immunity...
September 1, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/28937974/high-somatic-mutation-and-neoantigen-burden-are-correlated-with-decreased-progression-free-survival-in-multiple-myeloma
#9
A Miller, Y Asmann, L Cattaneo, E Braggio, J Keats, D Auclair, S Lonial, S J Russell, A K Stewart
Tumor-specific mutations can result in immunogenic neoantigens, both of which have been correlated with responsiveness to immune checkpoint inhibitors in highly mutagenic cancers. However, early results of single-agent checkpoint inhibitors in multiple myeloma (MM) have been underwhelming. Therefore, we sought to understand the relationship between mutation and neoantigen landscape of MM patients and responsiveness to therapies. Somatic mutation burden, neoantigen load, and response to therapy were determined using interim data from the MMRF CoMMpass study (NCT01454297) on 664 MM patients...
September 22, 2017: Blood Cancer Journal
https://www.readbyqxmd.com/read/28931635/a-computational-multiscale-agent-based-model-for-simulating-spatio-temporal-tumour-immune-response-to-pd1-and-pdl1-inhibition
#10
Chang Gong, Oleg Milberg, Bing Wang, Paolo Vicini, Rajesh Narwal, Lorin Roskos, Aleksander S Popel
When the immune system responds to tumour development, patterns of immune infiltrates emerge, highlighted by the expression of immune checkpoint-related molecules such as PDL1 on the surface of cancer cells. Such spatial heterogeneity carries information on intrinsic characteristics of the tumour lesion for individual patients, and thus is a potential source for biomarkers for anti-tumour therapeutics. We developed a systems biology multiscale agent-based model to capture the interactions between immune cells and cancer cells, and analysed the emergent global behaviour during tumour development and immunotherapy...
September 2017: Journal of the Royal Society, Interface
https://www.readbyqxmd.com/read/28912897/genomic-analysis-of-tumor-microenvironment-immune-types-across-14-solid-cancer-types-immunotherapeutic-implications
#11
Yu-Pei Chen, Yu Zhang, Jia-Wei Lv, Ying-Qin Li, Ya-Qin Wang, Qing-Mei He, Xiao-Jing Yang, Ying Sun, Yan-Ping Mao, Jing-Ping Yun, Na Liu, Jun Ma
We performed a comprehensive immuno-genomic analysis of tumor microenvironment immune types (TMITs), which is classified into four groups based on PD-L1+CD8A or PD-L1+cytolytic activity (CYT) expression, across a broad spectrum of solid tumors in order to help identify patients who will benefit from anti- PD-1/PD-L1 therapy. The mRNA sequencing data from The Cancer Genome Atlas (TCGA) of 14 solid cancer types representing 6,685 tumor samples was analyzed. TMIT was classified only for those tumor types that both PD-L1 and CD8A/CYT could prefict mutation and/or neoantigen number...
2017: Theranostics
https://www.readbyqxmd.com/read/28899059/targeting-neoantigens-in-glioblastoma-an-overview-of-cancer-immunogenomics-and-translational-implications
#12
Tanner M Johanns, Jay A Bowman-Kirigin, Connor Liu, Gavin P Dunn
No abstract text is available yet for this article.
September 1, 2017: Neurosurgery
https://www.readbyqxmd.com/read/28877075/microsatellite-instability-a-predictive-biomarker-for-cancer-immunotherapy
#13
Liisa Chang, Minna Chang, Hanna M Chang, Fuju Chang
Immunotherapy has shown promising results in various types of cancers. Checkpoint inhibitor drugs developed for cancer immunotherapy have been approved by the US Food and Drug Administration (FDA) for patients with advanced melanoma, non-small cell lung cancer, renal cell carcinoma, bladder cancers, and refractory Hodgkin lymphoma. In the latest announcement, the FDA has granted accelerated approval to pembrolizumab for pediatric and adult patients with microsatellite instability-high (MSI-H) or mismatch repair-deficient solid tumors...
September 4, 2017: Applied Immunohistochemistry & Molecular Morphology: AIMM
https://www.readbyqxmd.com/read/28874554/effects-of-thymic-selection-on-t-cell-recognition-of-foreign-and-tumor-antigenic-peptides
#14
Jason T George, David A Kessler, Herbert Levine
The advent of cancer immunotherapy has generated renewed hope for the treatment of many malignancies by introducing a number of novel strategies that exploit various properties of the immune system. These therapies are based on the idea that cytotoxic T lymphocytes (CTLs) directly recognize and respond to tumor-associated neoantigens (TANs) in much the same way as they would to foreign peptides presented on cell surfaces. To date, however, nearly all attempts to optimize immunotherapeutic strategies have been empirical...
September 19, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28867556/neoantigen-vaccines-pass-the-immunogenicity-test
#15
Gerald P Linette, Beatriz M Carreno
Neoantigens arising from tumor-specific genomic alterations constitute authentic non-self antigens and represent a new class of targets for cancer immunotherapy. Recent reports on various vaccine platforms targeting neoantigens suggest a basis for precision therapies customized to each patient's tumor mutational profile.
October 2017: Trends in Molecular Medicine
https://www.readbyqxmd.com/read/28864725/the-challenge-for-development-of-valuable-immuno-oncology-biomarkers
#16
EDITORIAL
Janice M Mehnert, Arta M Monjazeb, Johanna M T Beerthuijzen, Deborah Collyar, Larry Rubinstein, Lyndsay N Harris
The development of immunotherapy is an important breakthrough for the treatment of cancer, with antitumor efficacy observed in a wide variety of tumors. To optimize immunotherapy use, approaches must be developed to identify which patients are likely to achieve benefit. To minimize therapeutic toxicities and costs, understanding the ideal choice and sequencing of the numerous immuno-oncology agents available for individual patients is thus critical, but fraught with challenges. The immune tumor microenvironment (TME) is a unique aspect of the response to immuno-oncology agents and measurement of single biomarkers does not adequately capture these complex interactions...
September 1, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28857666/cancer-vaccines-enhanced-immunogenic-modulation-through-therapeutic-combinations
#17
Margaret E Gatti-Mays, Jason M Redman, Julie M Collins, Marijo Bilusic
Therapeutic cancer vaccines have gained significant popularity in recent years as new approaches for specific oncologic indications emerge. Three therapeutic cancer vaccines are FDA approved and one is currently approved by the EMA as monotherapy with modest treatment effects. Combining therapeutic cancer vaccines with other treatment modalities like radiotherapy (RT), hormone therapy, immunotherapy, and/or chemotherapy have been investigated as a means to enhance immune response and treatment efficacy. There is growing preclinical and clinical data that combination of checkpoint inhibitors and vaccines can induce immunogenic intensification with favorable outcomes...
August 31, 2017: Human Vaccines & Immunotherapeutics
https://www.readbyqxmd.com/read/28846956/hypermutated-tumours-in-the-era-of-immunotherapy-the-paradigm-of-personalised-medicine
#18
REVIEW
Laetitia Nebot-Bral, David Brandao, Loic Verlingue, Etienne Rouleau, Olivier Caron, Emmanuelle Despras, Yolla El-Dakdouki, Stéphane Champiat, Said Aoufouchi, Alexandra Leary, Aurélien Marabelle, David Malka, Nathalie Chaput, Patricia L Kannouche
Immune checkpoint inhibitors have demonstrated unprecedented clinical activity in a wide range of cancers. Significant therapeutic responses have recently been observed in patients presenting mismatch repair-deficient (MMRD) tumours. MMRD cancers exhibit a remarkably high rate of mutations, which can result in the formation of neoantigens, hypothesised to enhance the antitumour immune response. In addition to MMRD tumours, cancers mutated in the exonuclease domain of the catalytic subunit of the DNA polymerase epsilon (POLE) also exhibit an ultramutated genome and are thus likely to benefit from immunotherapy...
October 2017: European Journal of Cancer
https://www.readbyqxmd.com/read/28846477/modified-vaccinia-virus-ankara-based-vaccines-in-the-era-of-personalized-immunotherapy-of-cancer
#19
Kaïdre Bendjama, Eric Quemeneur
While interest in immunotherapies is renewed by the successful introduction of immune checkpoint blocking agent in the clinic, advances in genome sequencing are opening new possibilities in the design of increasingly personalized vaccines. Personalization of medicine can now be realistically contemplated at the single patient level. Unlike the previous generation of cancer vaccines, neoantigen directed vaccines would target truly specific tumor antigens resulting from acquired tumor genome mutations. Immune response induced by this next generation vaccine would not be subject to self-tolerance and will likely result to enhanced efficacy...
September 2, 2017: Human Vaccines & Immunotherapeutics
https://www.readbyqxmd.com/read/28813655/making-it-personal-neoantigen-vaccines-in-metastatic-melanoma
#20
Matthew D Hellmann, Alexandra Snyder
Somatic mutations in cancer can be translated into peptides, termed neoantigens, which can be recognized by the immune system as "foreign" epitopes. Two recent studies in Nature (Sahin et al., 2017; Ott et al., 2017) examine the effects of neoantigen vaccines on patients with stage III or IV melanoma and demonstrate immunogenicity and intriguing clinical safety and efficacy data in phase I studies.
August 15, 2017: Immunity
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