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Neoantigens

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https://www.readbyqxmd.com/read/28931635/a-computational-multiscale-agent-based-model-for-simulating-spatio-temporal-tumour-immune-response-to-pd1-and-pdl1-inhibition
#1
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/28920005/the-frequency-of-neoantigens-per-somatic-mutation-rather-than-overall-mutational-load-or-number-of-predicted-neoantigens-per-se-is-a-prognostic-factor-in-ovarian-clear-cell-carcinoma
#2
Hirokazu Matsushita, Kosei Hasegawa, Katsutoshi Oda, Shogo Yamamoto, Akira Nishijima, Yuichi Imai, Kayo Asada, Yuji Ikeda, Takahiro Karasaki, Keiichi Fujiwara, Hiroyuki Aburatani, Kazuhiro Kakimi
Neoantigens derived from tumor-specific somatic mutations are excellent targets for anti-tumor immune responses. In ovarian clear cell carcinoma (OCCC), checkpoint blockade yields durable responses in a subset of patients. To approach the question of why only some patients respond, we first investigated neoantigen loads and immune signatures using exome sequencing and expression array data for 74 OCCC patients treated conventionally. Neither the number of missense mutations nor total predicted neoantigens assessed in the tumor correlated with clinical outcomes...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28916749/checkpoint-blockade-immunotherapy-reshapes-the-high-dimensional-phenotypic-heterogeneity-of-murine-intratumoural-neoantigen-specific-cd8-t-cells
#3
M Fehlings, Y Simoni, H L Penny, E Becht, C Y Loh, M M Gubin, J P Ward, S C Wong, R D Schreiber, E W Newell
The analysis of neoantigen-specific CD8(+) T cells in tumour-bearing individuals is challenging due to the small pool of tumour antigen-specific T cells. Here we show that mass cytometry with multiplex combinatorial tetramer staining can identify and characterize neoantigen-specific CD8(+) T cells in mice bearing T3 methylcholanthrene-induced sarcomas that are susceptible to checkpoint blockade immunotherapy. Among 81 candidate antigens tested, we identify T cells restricted to two known neoantigens simultaneously in tumours, spleens and lymph nodes in tumour-bearing mice...
September 15, 2017: Nature Communications
https://www.readbyqxmd.com/read/28912897/genomic-analysis-of-tumor-microenvironment-immune-types-across-14-solid-cancer-types-immunotherapeutic-implications
#4
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
#5
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/28898209/neoantigen-prediction-and-the-need-for-validation
#6
Antonella Vitiello, Maurizio Zanetti
No abstract text is available yet for this article.
September 11, 2017: Nature Biotechnology
https://www.readbyqxmd.com/read/28891866/passive-transfer-autoimmunity-in-a-mouse-model-of-complex-regional-pain-syndrome
#7
Tian-Zhi Guo, Xiaoyou Shi, Wen-Wu Li, Tzuping Wei, J David Clark, Wade S Kingery
It has been proposed that Complex Regional Pain Syndrome (CRPS) is a post-traumatic autoimmune disease and we previously observed that B cells are required for the full expression of CRPS-like changes a mouse tibia fracture CRPS model. The current study used the mouse model to evaluate the progression of post-fracture CRPS-like changes in wildtype (WT) and muMT fracture mice lacking B cells and antibodies. The pronociceptive effects of injecting WT fracture mouse serum antibodies into muMT fracture mice were also evaluated...
September 1, 2017: Pain
https://www.readbyqxmd.com/read/28877075/microsatellite-instability-a-predictive-biomarker-for-cancer-immunotherapy
#8
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
#9
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 5, 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
#10
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.
August 31, 2017: Trends in Molecular Medicine
https://www.readbyqxmd.com/read/28864725/the-challenge-for-development-of-valuable-immuno-oncology-biomarkers
#11
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/28860189/the-major-histocompatibility-complex-class-i-immunopeptidome-of-extracellular-vesicles
#12
Silvia A Synowsky, Sally L Shirran, Fiona G M Cooke, Antony N Antoniou, Catherine H Botting, Simon J Powis
Extracellular vesicles (EVs) are released by most cell types and have been associated with multiple immunomodulatory functions. MHC class I molecules have crucial roles in antigen presentation and in eliciting immune responses and are known to be incorporated into EVs. However, the MHC class I immunopeptidome of EVs has not been established. Here, using a small-scale immunoisolation of the antigen serotypes HLA-A*02:01 and HLA-B*27:05 expressed on the Epstein-Barr virus-transformed B cell line Jesthom and MS of the eluted peptides from both cells and EVs, we identified 516 peptides that bind either HLA-A*02:01 or HLA-B*27:05...
August 31, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28857666/cancer-vaccines-enhanced-immunogenic-modulation-through-therapeutic-combinations
#13
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
#14
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...
August 24, 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
#15
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...
August 28, 2017: Human Vaccines & Immunotherapeutics
https://www.readbyqxmd.com/read/28835723/targeting-neoantigens-to-augment-antitumour-immunity
#16
Mark Yarchoan, Burles A Johnson, Eric R Lutz, Daniel A Laheru, Elizabeth M Jaffee
No abstract text is available yet for this article.
August 24, 2017: Nature Reviews. Cancer
https://www.readbyqxmd.com/read/28813655/making-it-personal-neoantigen-vaccines-in-metastatic-melanoma
#17
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
https://www.readbyqxmd.com/read/28802495/the-immunology-of-melanoma
#18
REVIEW
Jennifer S Ko
The relatively high DNA mutational burden in melanoma allows for the creation of potentially "foreign," immune-stimulating neoantigens, and leads to its exceptional immunogenicity. Brisk tumor-infiltrating lymphocytes, a marker of immune editing, confer improved overall survival in melanoma, possibly due to reduced sentinel lymph node spread. Meanwhile, T-cell-stimulating drugs, so-called T-cell checkpoint inhibitors, which reverse peripheral tolerance-dependent tumor escape, have demonstrated unparalleled clinical success in metastatic melanoma...
September 2017: Clinics in Laboratory Medicine
https://www.readbyqxmd.com/read/28770222/mismatch-repair-deficiency-as-a-predictive-biomarker-for-immunotherapy-efficacy
#19
REVIEW
Giulia Viale, Dario Trapani, Giuseppe Curigliano
Immunotherapy has revolutionized cancer treatment. Immune-checkpoint inhibitors, on balance, showed a favorable efficacy/toxicity profile with durable response in different cancer types. No predictive biomarker has been validated thus far to select patients who would benefit from therapy. Among the candidate predictive biomarkers, mismatch repair status of the tumor is currently one of the most promising. Indeed, tumors displaying mismatch repair deficiency or microsatellite instability showed remarkable response to immunotherapy in clinical trials...
2017: BioMed Research International
https://www.readbyqxmd.com/read/28761058/heterogeneity-of-tumor-infiltrating-lymphocytes-ascribed-to-local-immune-status-rather-than-neoantigens-by-multi-omics-analysis-of-glioblastoma-multiforme
#20
Lin Feng, Haipeng Qian, Xuexin Yu, Kan Liu, Ting Xiao, Chengli Zhang, Manchao Kuang, Shujun Cheng, Xueji Li, Jinghai Wan, Kaitai Zhang
Hypothetically, intratumoral genomic heterogeneity has the potential to foster tumor-infiltrating lymphocyte (TIL) diversity; however, no study has directly tested this hypothesis by simultaneously investigating somatic mutations, TIL diversity, and immune response activity. Thus, we performed whole-exome sequencing, immune repertoire sequencing and gene expression on ten spatially separated tumor samples obtained from two tumor masses excised from a glioblastoma multiforme (GBM) patient, and we included peripheral blood as control...
July 31, 2017: Scientific Reports
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