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Cancer neoantigens

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https://www.readbyqxmd.com/read/28431188/t-cell-receptor-%C3%AE-chain-repertoire-analysis-reveals-the-association-between-neoantigens-and-tumour-infiltrating-lymphocytes-in-multifocal-papillary-thyroid-carcinoma
#1
Zheming Lu, Chaoting Zhang, Jindong Sheng, Jing Shen, Baoguo Liu
To explore whether a few non-synonymous somatic mutations could induce activation and proliferation of neoantigen-specific tumour-infiltrating lymphocytes (TILs) in tumours with low mutation rates, we analysed a patient with multifocal papillary thyroid carcinoma (seven non-contiguous cancer foci) to investigate the relationship between neoantigens and TILs. These seven foci had a few or no non-synonymous somatic mutations; moreover, multiple loci had similar or different spectra of mutations. We used high-throughput sequencing of the rearranged genes in T cell receptor β-chain (TCRβ) to reveal the basic characteristics of T cells in seven tumour foci and matched adjacent normal tissue...
April 21, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/28428277/immune-gene-expression-is-associated-with-genomic-aberrations-in-breast-cancer
#2
Anton Safonov, Tingting Jiang, Giampaolo Bianchini, Balázs Győrffy, Thomas Karn, Christos Hatzis, Lajos Pusztai
The presence of tumor-infiltrating lymphocytes (TIL) is a favorable prognostic factor in breast cancer, but what drives immune infiltration remains unknown. Here we examine if clonal heterogeneity, total mutation load, neoantigen load, copy number variations (CNV), gene- or pathway-level somatic mutations, or germline polymorphisms (SNP) are associated with immune metagene expression in breast cancer subtypes. Thirteen published immune metagenes correlated separately with genomic metrics in the 3 major breast cancer subtypes...
April 20, 2017: Cancer Research
https://www.readbyqxmd.com/read/28423700/hla-class-i-loss-in-metachronous-metastases-prevents-continuous-t-cell-recognition-of-mutated-neoantigens-in-a-human-melanoma-model
#3
Barbara Schrörs, Silke Lübcke, Volker Lennerz, Martina Fatho, Anne Bicker, Catherine Wölfel, Patrick Derigs, Thomas Hankeln, Dirk Schadendorf, Annette Paschen, Thomas Wölfel
T lymphocytes against tumor-specific mutated neoantigens can induce tumor regression. Also, the size of the immunogenic cancer mutanome is supposed to correlate with the clinical efficacy of checkpoint inhibition. Herein, we studied the susceptibility of tumor cell lines from lymph node metastases occurring in a melanoma patient over several years towards blood-derived, neoantigen-specific CD8+ T cells. In contrast to a cell line established during early stage III disease, all cell lines generated at later time points from stage IV metastases exhibited partial or complete loss of HLA class I expression...
March 9, 2017: Oncotarget
https://www.readbyqxmd.com/read/28410302/tumor-infiltrating-lymphocyte-therapy-and-neoantigens
#4
Paul F Robbins
The adoptive cell transfer (ACT) of autologous tumor-infiltrating lymphocytes has been shown to be effective at mediating tumor regression in more than half of patients with metastatic melanoma and in mediating long-term complete regression in approximately one fourth of all patients with this cancer. The success of this approach in patients with cholangiocarcinoma and colon cancer supports efforts to expand ACT therapies to treatment of patients bearing a wide array of cancer types. Recent improvements in deep sequencing of the patient cancers, combined with extensive immunological testing of autologous tumor-infiltrating lymphocytes, indicate that T cells targeting epitopes arising from nonsynonymous somatic mutations, termed neoantigens, play important roles in mediating many of the effective cancer immunotherapies seen in response to ACT...
March 2017: Cancer Journal
https://www.readbyqxmd.com/read/28410301/dendritic-cell-strategies-for-eliciting-mutation-derived-tumor-antigen-responses-in-patients
#5
Sreekumar Balan, John Finnigan, Nina Bhardwaj
Dendritic cells (DCs) are equipped for sensing danger signals and capturing, processing, and presenting antigens to naive or effector cells and are critical in inducing humoral and adaptive immunity. Successful vaccinations are those that activate DCs to elicit both cellular and humoral responses, as well as long-lasting memory response against the target of interest. Recently, it has become apparent that tumor cells can provide new sources of antigens through nonsynonymous mutations or frame-shift mutations, leading to potentially hundreds of mutation-derived tumor antigens (MTAs) or neoantigens...
March 2017: Cancer Journal
https://www.readbyqxmd.com/read/28410300/applied-cancer-immunogenomics-leveraging-neoantigen-discovery-in-glioblastoma
#6
Tanner M Johanns, Gavin P Dunn
Glioblastoma (GBM) remains a significant cause of cancer-related mortality in pediatric and adult patients with limited treatment options. Immunotherapy represents a promising new therapeutic approach in many solid and hematologic malignancies, including GBM, although only a subset of patients responds clinically. Thus, current efforts are focused on identifying patients most likely to benefit from immune-based therapies. The cancer immunogenomics approach identifies candidate neoantigens from genomics information and represents a potentially exciting new space in precision neuro-oncology...
March 2017: Cancer Journal
https://www.readbyqxmd.com/read/28410296/neoantigen-discovery-in-human-cancers
#7
Elaine R Mardis
Cancer is caused by alterations to DNA that ultimately are translated into altered proteins with unique amino acid sequences when compared with their counterparts in normal cells. By inference, these altered proteins have the potential to elicit immune responses such as T-cell recognition, if properly presented by the immune system following protein degradation and major histocompatibility complex binding. Historically, identifying tumor-specific mutant antigens was painstaking work that involved molecular cloning and immune screening...
March 2017: Cancer Journal
https://www.readbyqxmd.com/read/28408606/landscape-of-immunogenic-tumor-antigens-in-successful-immunotherapy-of-virally-induced-epithelial-cancer
#8
Sanja Stevanović, Anna Pasetto, Sarah R Helman, Jared J Gartner, Todd D Prickett, Bryan Howie, Harlan S Robins, Paul F Robbins, Christopher A Klebanoff, Steven A Rosenberg, Christian S Hinrichs
Immunotherapy has clinical activity in certain virally associated cancers. However, the tumor antigens targeted in successful treatments remain poorly defined. We used a personalized immunogenomic approach to elucidate the global landscape of antitumor T cell responses in complete regression of human papillomavirus-associated metastatic cervical cancer after tumor-infiltrating adoptive T cell therapy. Remarkably, immunodominant T cell reactivities were directed against mutated neoantigens or a cancer germline antigen, rather than canonical viral antigens...
April 14, 2017: Science
https://www.readbyqxmd.com/read/28404974/tumor-immunotherapy-drug-induced-neoantigens-xenogenization-and-immune-checkpoint-inhibitors
#9
Ornella Franzese, Francesco Torino, Maria Pia Fuggetta, Angelo Aquino, Mario Roselli, Enzo Bonmassar, Anna Giuliani, Stefania D'Atri
More than 40 years ago, we discovered that novel transplantation antigens can be induced in vivo or in vitro by treating murine leukemia with dacarbazine. Years later, this phenomenon that we called "Chemical Xenogenization" (CX) and more recently, "Drug-Induced Xenogenization" (DIX), was reproduced by Thierry Boon with a mutagenic/carcinogenic compound (i.e. N-methyl-N'-nitro-N-nitrosoguanidine). In both cases, the molecular bases of DIX rely on mutagenesis induced by methyl adducts to oxygen-6 of DNA guanine...
March 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/28403580/correction-membrane-associated-cancer-oocyte-neoantigen-sas1b-ovastacin-is-a-candidate-immunotherapeutic-target-for-uterine-tumors
#10
Eusebio S Pires, Ryan S D'Souza, Marisa A Needham, Austin K Herr, Amir A Jazaeri, Hui Li, Mark H Stoler, Kiley L Anderson-Knapp, Theodore Thomas, Arabinda Mandal, Alain Gougeon, Charles J Flickinger, David E Bruns, Brian A Pollok, John C Herr
No abstract text is available yet for this article.
February 28, 2017: Oncotarget
https://www.readbyqxmd.com/read/28389595/cancer-immunogenomics-computational-neoantigen-identification-and-vaccine-design
#11
Jasreet Hundal, Christopher A Miller, Malachi Griffith, Obi L Griffith, Jason Walker, Susanna Kiwala, Aaron Graubert, Joshua McMichael, Adam Coffman, Elaine R Mardis
The application of modern high-throughput genomics to the study of cancer genomes has exploded in the past few years, yielding unanticipated insights into the myriad and complex combinations of genomic alterations that lead to the development of cancers. Coincident with these genomic approaches have been computational analyses that are capable of multiplex evaluations of genomic data toward specific therapeutic end points. One such approach is called "immunogenomics" and is now being developed to interpret protein-altering changes in cancer cells in the context of predicted preferential binding of these altered peptides by the patient's immune molecules, specifically human leukocyte antigen (HLA) class I and II proteins...
April 7, 2017: Cold Spring Harbor Symposia on Quantitative Biology
https://www.readbyqxmd.com/read/28382562/biomarkers-to-predict-prognosis-and-response-to-checkpoint-inhibitors
#12
REVIEW
Takeshi Yuasa, Hitoshi Masuda, Shinya Yamamoto, Noboru Numao, Junji Yonese
Nivolumab is a fully human immunoglobulin (Ig) G4 antibody that selectively inhibits the programmed death 1 (PD-1) immune checkpoint molecule, and has recently been launched for the treatment of renal cell cancer (RCC) in Japan. Based on its promising anti-tumor efficacy and manageable safety profile demonstrated in the phase III Checkmate 025 trial, nivolumab therapy is rapidly being introduced in metastatic RCC clinical practice. The phase Ia study of atezolizumab, which is a humanized anti-PD-ligand 1 (PD-L1) monoclonal IgG1 antibody, also demonstrated excellent treatment results...
April 5, 2017: International Journal of Clinical Oncology
https://www.readbyqxmd.com/read/28371614/hypermutations-in-gliomas-a-potential-immunotherapy-target
#13
Gaetano Finocchiaro, Tiziana Langella, Cristina Corbetta, Serena Pellegatta
Checkpoint inhibitors, like ipilimumab, nivolumab, and pembrolizumab, have provided a breakthrough in cancer immunotherapy, such as in the treatment of melanoma and colorectal and lung cancer. The close relationship between the number of mutations (mutational load) and the response to checkpoint immunotherapy has been convincingly demonstrated in these cancers. Hypermutations in tumors are caused by environmental factors, like UV radiations or cigarette smoking, or by germinal mutations affecting genes of the Mismatch Repair (MMR) machinery, as in the Lynch syndrome...
February 2017: Discovery Medicine
https://www.readbyqxmd.com/read/28366678/harnessing-the-immunotherapy-revolution-for-the-treatment-of-childhood-cancers
#14
REVIEW
Robbie G Majzner, Sabine Heitzeneder, Crystal L Mackall
Cancer immunotherapies can be classified into agents that amplify natural immune responses (e.g., checkpoint inhibitors) versus synthetic immunotherapies designed to initiate new responses (e.g., monoclonal antibodies [mAbs], chimeric antigen receptors [CARs]). Checkpoint inhibitors mediate unprecedented benefit in some adult cancers, but have not demonstrated significant activity in pediatric cancers, likely due their paucity of neoantigens. In contrast, synthetic immunotherapies such as mAbs and CAR T cells demonstrate impressive effects against childhood cancers...
April 10, 2017: Cancer Cell
https://www.readbyqxmd.com/read/28363643/genetic-features-of-aflatoxin-associated-hepatocellular-carcinomas
#15
Weilong Zhang, Huan He, Mengya Zang, Qifeng Wu, Hong Zhao, Ling-Ling Lu, Peiqing Ma, Hongwei Zheng, Nengjin Wang, Ying Zhang, Siyuan He, Xiaoyan Chen, Zhiyuan Wu, Xiaoyue Wang, Jianqiang Cai, Zhihua Liu, Zongtang Sun, Yi-Xin Zeng, Chunfeng Qu, Yuchen Jiao
BACKGROUND & AIMS: Dietary exposure to aflatoxin is an important risk factor for hepatocellular carcinoma (HCC). However, little is known about the genomic features and mutations of aflatoxin-associated HCCs compared with HCCs not associated with aflatoxin exposure. We investigated the genetic features of aflatoxin-associated HCC that can be used to differentiate them from HCCs not associated with this carcinogen. METHODS: We obtained HCC tumor tissues and matched non-tumor liver tissues from 49 patients, collected from 1990 through 2016, at the Qidong Liver Cancer Hospital Institute in China-a high-risk region for aflatoxin exposure (38...
March 28, 2017: Gastroenterology
https://www.readbyqxmd.com/read/28344893/integrated-analysis-of-somatic-mutations-and-immune-microenvironment-in-malignant-pleural-mesothelioma
#16
Kazuma Kiyotani, Jae-Hyun Park, Hiroyuki Inoue, Aliya Husain, Sope Olugbile, Makda Zewde, Yusuke Nakamura, Wickii T Vigneswaran
To investigate the link between the genomic landscape of cancer cells and immune microenvironment in tumor tissues, we characterized somatic mutations and tumor-infiltrating lymphocytes (TILs) in malignant pleural mesothelioma (MPM), including mutation/neoantigen load, spatial heterogeneity of somatic mutations of cancer cells and TILs (T-cell receptor β (TCRβ) repertoire), and expression profiles of immune-related genes using specimens of three different tumor sites (anterior, posterior, and diaphragm) obtained from six MPM patients...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28344870/immunological-profiling-of-molecularly-classified-high-risk-endometrial-cancers-identifies-pole-mutant-and-microsatellite-unstable-carcinomas-as-candidates-for-checkpoint-inhibition
#17
Florine A Eggink, Inge C Van Gool, Alexandra Leary, Pamela M Pollock, Emma J Crosbie, Linda Mileshkin, Ekaterina S Jordanova, Julien Adam, Luke Freeman-Mills, David N Church, Carien L Creutzberg, Marco De Bruyn, Hans W Nijman, Tjalling Bosse
High-risk endometrial cancer (EC) is an aggressive disease for which new therapeutic options are needed. Aims of this study were to validate the enhanced immune response in highly mutated ECs and to explore immune profiles in other EC subgroups. We evaluated immune infiltration in 116 high-risk ECs from the TransPORTEC consortium, previously classified into four molecular subtypes: (i) ultramutated POLE exonuclease domain-mutant ECs (POLE-mutant); (ii) hypermutated microsatellite unstable (MSI); (iii) p53-mutant; and (iv) no specific molecular profile (NSMP)...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28344865/identification-of-genetic-determinants-of-breast-cancer-immune-phenotypes-by-integrative-genome-scale-analysis
#18
Wouter Hendrickx, Ines Simeone, Samreen Anjum, Younes Mokrab, François Bertucci, Pascal Finetti, Giuseppe Curigliano, Barbara Seliger, Luigi Cerulo, Sara Tomei, Lucia Gemma Delogu, Cristina Maccalli, Ena Wang, Lance D Miller, Francesco M Marincola, Michele Ceccarelli, Davide Bedognetti
Cancer immunotherapy is revolutionizing the clinical management of several tumors, but has demonstrated limited activity in breast cancer. The development of more effective treatments is hindered by incomplete knowledge of the genetic determinant of immune responsiveness. To fill this gap, we mined copy number alteration, somatic mutation, and expression data from The Cancer Genome Atlas (TCGA). By using RNA-sequencing data from 1,004 breast cancers, we defined distinct immune phenotypes characterized by progressive expression of transcripts previously associated with immune-mediated rejection...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28340323/a-key-to-the-backdoor-into-the-castle-the-clinical-ramifications-of-immunoediting-driven-by-antigenic-competition
#19
M G Hanna, Jason David Howard
Over the last decade the field of cancer biology has gained considerable data on genomic heterogeneity. This situation creates challenges and possibly opportunities for cancer treatment. The evolution of the tumor at all stages also requires the growing malignancy to confront and avoid the immune system. What we describe here is the interaction of two immune phenomena that work together to change the characteristics of the tumor, i.e., antigenic competition and immune editing. These two systems are mutually functional and their interaction is capable of altering the characteristics of the tumor for protection and survival in an immune competent host as well as restricting the diversity of the tumor clones...
March 24, 2017: Human Vaccines & Immunotherapeutics
https://www.readbyqxmd.com/read/28329770/antigen-presentation-profiling-reveals-recognition-of-lymphoma-immunoglobulin-neoantigens
#20
Michael S Khodadoust, Niclas Olsson, Lisa E Wagar, Ole A W Haabeth, Binbin Chen, Kavya Swaminathan, Keith Rawson, Chih Long Liu, David Steiner, Peder Lund, Samhita Rao, Lichao Zhang, Caleb Marceau, Henning Stehr, Aaron M Newman, Debra K Czerwinski, Victoria E H Carlton, Martin Moorhead, Malek Faham, Holbrook E Kohrt, Jan Carette, Michael R Green, Mark M Davis, Ronald Levy, Joshua E Elias, Ash A Alizadeh
Cancer somatic mutations can generate neoantigens that distinguish malignant from normal cells. However, the personalized identification and validation of neoantigens remains a major challenge. Here we discover neoantigens in human mantle-cell lymphomas by using an integrated genomic and proteomic strategy that interrogates tumour antigen peptides presented by major histocompatibility complex (MHC) class I and class II molecules. We applied this approach to systematically characterize MHC ligands from 17 patients...
March 30, 2017: Nature
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