keyword
https://read.qxmd.com/read/38518448/effect-of-dapagliflozin-on-collectins-and-complement-activation-in-plasma-from-patients-with-type-2-diabetes-and-albuminuria-data-from-the-dapkid-cohort
#1
JOURNAL ARTICLE
Mia Jensen, Mie K Eickhoff, Frederik Persson, Peter Rossing, Steffen Thiel, Søren W K Hansen, Yaseelan Palarasah, Per Svenningsen, Boye L Jensen
BACKGROUND: Sodium-glucose cotransporter 2 (SGLT- 2) inhibitors exert cardiovascular and kidney-protective effects in people with diabetes. Attenuation of inflammation could be important for systemic protection. The lectin pathway of complement system activation is linked to diabetic nephropathy. We hypothesized that SGLT-2 inhibitors lower the circulating level of pattern-recognition molecules of the lectin cascade and attenuate systemic complement activation. METHODS: Analysis of paired plasma samples from the DapKid crossover intervention study where patients with type 2 diabetes mellitus (T2DM) and albuminuria were treated with dapagliflozin and placebo for 12 weeks (10 mg/day, n=36)...
March 15, 2024: Immunobiology
https://read.qxmd.com/read/38508656/circular-rna-as-a-source-of-neoantigens-for-cancer-vaccines
#2
JOURNAL ARTICLE
Yi Ren, Thamizhanban Manoharan, Beijia Liu, Cyrus Zai Ming Cheng, Bei En Siew, Wai-Kit Cheong, Kai Yin Lee, Ian Jse-Wei Tan, Bettina Lieske, Ker-Kan Tan, Gloryn Chia
BACKGROUND: The effectiveness of somatic neoantigen-based immunotherapy is often hindered by the limited number of mutations in tumors with low to moderate mutation burden. Focusing on microsatellite-stable colorectal cancer (CRC), this study investigates the potential of tumor-associated circular RNAs (circRNAs) as an alternative source of neoepitopes in CRC. METHODS: Tumor-associated circRNAs in CRC were identified using the MiOncoCirc database and ribo-depletion RNA sequencing of paired clinical normal and tumor samples...
March 19, 2024: Journal for Immunotherapy of Cancer
https://read.qxmd.com/read/38480738/dendritic-cell-targeted-therapy-expands-cd8-t-cell-responses-to-bona-fide-neoantigens-in-lung-tumors
#3
JOURNAL ARTICLE
Lucía López, Luciano Gastón Morosi, Federica La Terza, Pierre Bourdely, Giuseppe Rospo, Roberto Amadio, Giulia Maria Piperno, Valentina Russo, Camilla Volponi, Simone Vodret, Sonal Joshi, Francesca Giannese, Dejan Lazarevic, Giovanni Germano, Patrizia Stoitzner, Alberto Bardelli, Marc Dalod, Luigia Pace, Nicoletta Caronni, Pierre Guermonprez, Federica Benvenuti
Cross-presentation by type 1 DCs (cDC1) is critical to induce and sustain antitumoral CD8 T cell responses to model antigens, in various tumor settings. However, the impact of cross-presenting cDC1 and the potential of DC-based therapies in tumors carrying varied levels of bona-fide neoantigens (neoAgs) remain unclear. Here we develop a hypermutated model of non-small cell lung cancer in female mice, encoding genuine MHC-I neoepitopes to study neoAgs-specific CD8 T cell responses in spontaneous settings and upon Flt3L + αCD40 (DC-therapy)...
March 13, 2024: Nature Communications
https://read.qxmd.com/read/38451249/transcriptomic-profiling-of-plasma-extracellular-vesicles-enables-reliable-annotation-of-the-cancer-specific-transcriptome-and-molecular-subtype
#4
JOURNAL ARTICLE
Vahid Bahrambeigi, Jaewon J Lee, Vittorio Branchi, Kimal I Rajapakshe, Zhichao Xu, Naishu Kui, Jason T Henry, Kun Wang, Bret M Stephens, Sarah Dhebat, Mark W Hurd, Ryan Sun, Peng Yang, Eytan Ruppin, Wenyi Wang, Scott Kopetz, Anirban Maitra, Paola A Guerrero
Longitudinal monitoring of patients with advanced cancers is crucial to evaluate both disease burden and treatment response. Current liquid biopsy approaches mostly rely on the detection of DNA-based biomarkers. However, plasma RNA analysis can unleash tremendous opportunities for tumor state interrogation and molecular subtyping. Through the application of deep learning algorithms to the deconvolved transcriptomes of RNA within plasma extracellular vesicles (evRNA), we successfully predict consensus molecular subtypes in metastatic colorectal cancer patients...
March 7, 2024: Cancer Research
https://read.qxmd.com/read/38426497/cancer-neoepitopes-viewed-through-negative-selection-and-peripheral-tolerance-a-new-path-to-cancer-vaccines
#5
REVIEW
Pramod K Srivastava
A proportion of somatic mutations in tumors create neoepitopes that can prime T cell responses that target the MHC I-neoepitope complexes on tumor cells, mediating tumor control or rejection. Despite the compelling centrality of neoepitopes to cancer immunity, we know remarkably little about what constitutes a neoepitope that can mediate tumor control in vivo and what distinguishes such a neoepitope from the vast majority of similar candidate neoepitopes that are inefficacious in vivo. Studies in mice as well as clinical trials have begun to reveal the unexpected paradoxes in this area...
March 1, 2024: Journal of Clinical Investigation
https://read.qxmd.com/read/38335301/estrogen-receptor-mutations-as-novel-targets-for-immunotherapy-in-metastatic-estrogen-receptor-positive-breast-cancer
#6
JOURNAL ARTICLE
Jonathan Goldberg, Na Qiao, Jennifer L Guerriero, Brett Gross, Yagiz Meneksedag, Yoshimi F Lu, Anne V Philips, Tasnim Rahman, Funda Meric-Bernstam, Jason Roszik, Ken Chen, Rinath Jeselsohn, Sara M Tolaney, George E Peoples, Gheath Alatrash, Elizabeth A Mittendorf
Estrogen receptor-positive (ER+) breast cancer is not considered immunogenic and, to date, has been proven resistant to immunotherapy. Endocrine therapy remains the cornerstone of treatment for ER+ breast cancers. However, constitutively activating mutations in the estrogen receptor alpha (ESR1) gene can emerge during treatment, rendering tumors resistant to endocrine therapy. Although these mutations represent a pathway of resistance, they also represent a potential source of neoepitopes that can be targeted by immunotherapy...
February 9, 2024: Cancer Res Commun
https://read.qxmd.com/read/38330990/vaccines-targeting-esr1-activating-mutations-elicit-anti-tumor-immune-responses-and-suppress-estrogen-signaling-in-therapy-resistant-er-breast-cancer
#7
JOURNAL ARTICLE
Gabrielle P Dailey, Christopher A Rabiola, Gangjun Lei, Junping Wei, Xiao-Yi Yang, Tao Wang, Cong-Xiao Liu, Melissa Gajda, Amy C Hobeika, Amanda Summers, Robert D Marek, Michael A Morse, Herbert K Lyerly, Erika J Crosby, Zachary C Hartman
ER+ breast cancers (BC) are characterized by the elevated expression and signaling of estrogen receptor alpha ( ESR1) , which renders them sensitive to anti-endocrine therapy. While these therapies are clinically effective, prolonged treatment inevitably results in therapeutic resistance, which can occur through the emergence of gain-of-function mutations in ESR1 . The central importance of ESR1 and development of mutated forms of ESR1 suggest that vaccines targeting these proteins could potentially be effective in preventing or treating endocrine resistance...
December 31, 2024: Human Vaccines & Immunotherapeutics
https://read.qxmd.com/read/38307904/mutation-specific-car-t-cells-as-precision-therapy-for-iglv3-21-r110-expressing-high-risk-chronic-lymphocytic-leukemia
#8
JOURNAL ARTICLE
Florian Märkl, Christoph Schultheiß, Murtaza Ali, Shih-Shih Chen, Marina Zintchenko, Lukas Egli, Juliane Mietz, Obinna Chijioke, Lisa Paschold, Sebastijan Spajic, Anne Holtermann, Janina Dörr, Sophia Stock, Andreas Zingg, Heinz Läubli, Ignazio Piseddu, David Anz, Marcus Dühren-von Minden, Tianjiao Zhang, Thomas Nerreter, Michael Hudecek, Susana Minguet, Nicholas Chiorazzi, Sebastian Kobold, Mascha Binder
The concept of precision cell therapy targeting tumor-specific mutations is appealing but requires surface-exposed neoepitopes, which is a rarity in cancer. B cell receptors (BCR) of mature lymphoid malignancies are exceptional in that they harbor tumor-specific-stereotyped sequences in the form of point mutations that drive self-engagement of the BCR and autologous signaling. Here, we use a BCR light chain neoepitope defined by a characteristic point mutation (IGLV3-21R110 ) for selective targeting of a poor-risk subset of chronic lymphocytic leukemia (CLL) with chimeric antigen receptor (CAR) T cells...
February 2, 2024: Nature Communications
https://read.qxmd.com/read/38306431/h3k27m-neoepitope-vaccination-in-diffuse-midline-glioma-induces-b-and-t-cell-responses-across-diverse-hla-loci-of-a-recovered-patient
#9
JOURNAL ARTICLE
Tamara Boschert, Kristina Kromer, Taga Lerner, Katharina Lindner, Gordon Haltenhof, Chin Leng Tan, Kristine Jähne, Isabel Poschke, Lukas Bunse, Philipp Eisele, Niklas Grassl, Iris Mildenberger, Katharina Sahm, Michael Platten, John M Lindner, Edward W Green
H3K27M, a driver mutation with T and B cell neoepitope characteristics, defines an aggressive subtype of diffuse glioma with poor survival. We functionally dissect the immune response of one patient treated with an H3K27M peptide vaccine who subsequently entered complete remission. The vaccine robustly expanded class II human leukocyte antigen (HLA)-restricted peripheral H3K27M-specific T cells. Using functional assays, we characterized 34 clonally unique H3K27M-reactive T cell receptors and identified critical, conserved motifs in their complementarity-determining region 3 regions...
February 2, 2024: Science Advances
https://read.qxmd.com/read/38297116/deepomics-ffpe-a-deep-neural-network-model-identifies-dna-sequencing-artifacts-from-formalin-fixed-paraffin-embedded-tissue-with-high-accuracy
#10
JOURNAL ARTICLE
Dong-Hyuk Heo, Inyoung Kim, Heejae Seo, Seong-Gwang Kim, Minji Kim, Jiin Park, Hongsil Park, Seungmo Kang, Juhee Kim, Soonmyung Paik, Seong-Eui Hong
Formalin-fixed, paraffin-embedded (FFPE) tissue specimens are routinely used in pathological diagnosis, but their large number of artifactual mutations complicate the evaluation of companion diagnostics and analysis of next-generation sequencing data. Identification of variants with low allele frequencies is challenging because existing FFPE filtering tools label all low-frequency variants as artifacts. To address this problem, we aimed to develop DEEPOMICS FFPE, an AI model that can classify a true variant from an artifact...
January 31, 2024: Scientific Reports
https://read.qxmd.com/read/38282550/exploring-co-occurring-pole-exonuclease-and-non-exonuclease-domain-mutations-and-their-impact-on-tumor-mutagenicity
#11
JOURNAL ARTICLE
Shreya M Shah, Elena V Demidova, Salena Ringenbach, Bulat Faezov, Mark Andrake, Arjun Gandhi, Pilar Mur, Julen Viana-Errasti, Joanne Xiu, Jeffrey Swensen, Laura Valle, Roland L Dunbrack, Michael J Hall, Sanjeevani Arora
UNLABELLED: POLE driver mutations in the exonuclease domain (ExoD driver) are prevalent in several cancers, including colorectal cancer and endometrial cancer, leading to dramatically ultra-high tumor mutation burden (TMB). To understand whether POLE mutations that are not classified as drivers (POLE Variant) contribute to mutagenesis, we assessed TMB in 447 POLE-mutated colorectal cancers, endometrial cancers, and ovarian cancers classified as TMB-high ≥10 mutations/Mb (mut/Mb) or TMB-low <10 mut/Mb...
January 26, 2024: Cancer Res Commun
https://read.qxmd.com/read/38279992/an-analysis-pipeline-for-understanding-6-thioguanine-effects-on-a-mouse-tumour-genome
#12
JOURNAL ARTICLE
Patricio Yankilevich, Loulieta Nazerai, Shona Caroline Willis, Kjeld Schmiegelow, Daniela De Zio, Morten Nielsen
Mouse tumour models are extensively used as a pre-clinical research tool in the field of oncology, playing an important role in anticancer drugs discovery. Accordingly, in cancer genomics research, the demand for next-generation sequencing (NGS) is increasing, and consequently, the need for data analysis pipelines is likewise growing. Most NGS data analysis solutions to date do not support mouse data or require highly specific configuration for their use. Here, we present a genome analysis pipeline for mouse tumour NGS data including the whole-genome sequence (WGS) data analysis flow for somatic variant discovery, and the RNA-seq data flow for differential expression, functional analysis and neoantigen prediction...
January 27, 2024: Cancer Immunology, Immunotherapy: CII
https://read.qxmd.com/read/38278991/a-fluid-biomarker-reveals-loss-of-tdp-43-splicing-repression-in-presymptomatic-als-ftd
#13
JOURNAL ARTICLE
Katherine E Irwin, Pei Jasin, Kerstin E Braunstein, Irika R Sinha, Mark A Garret, Kyra D Bowden, Koping Chang, Juan C Troncoso, Abhay Moghekar, Esther S Oh, Denitza Raitcheva, Dan Bartlett, Timothy Miller, James D Berry, Bryan J Traynor, Jonathan P Ling, Philip C Wong
Although loss of TAR DNA-binding protein 43 kDa (TDP-43) splicing repression is well documented in postmortem tissues of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD), whether this abnormality occurs during early-stage disease remains unresolved. Cryptic exon inclusion reflects loss of function of TDP-43, and thus detection of proteins containing cryptic exon-encoded neoepitopes in cerebrospinal fluid (CSF) or blood could reveal the earliest stages of TDP-43 dysregulation in patients...
January 26, 2024: Nature Medicine
https://read.qxmd.com/read/38243308/non-canonical-antigens-are-the-largest-fraction-of-peptides-presented-by-mhc-class-i-in-mismatch-repair-deficient-murine-colorectal-cancer
#14
JOURNAL ARTICLE
Giuseppe Rospo, Rosaria Chilà, Vittoria Matafora, Veronica Basso, Simona Lamba, Alice Bartolini, Angela Bachi, Federica Di Nicolantonio, Anna Mondino, Giovanni Germano, Alberto Bardelli
BACKGROUND: Immunotherapy based on checkpoint inhibitors is highly effective in mismatch repair deficient (MMRd) colorectal cancer (CRC). These tumors carry a high number of mutations, which are predicted to translate into a wide array of neoepitopes; however, a systematic classification of the neoantigen repertoire in MMRd CRC is lacking. Mass spectrometry peptidomics has demonstrated the existence of MHC class I associated peptides (MAPs) originating from non-coding DNA regions. Based on these premises we investigated DNA genomic regions responsible for generating MMRd-induced peptides...
January 19, 2024: Genome Medicine
https://read.qxmd.com/read/38238803/association-of-biochemical-markers-with-bone-marrow-lesion-changes-on-imaging-data-from-the-foundation-for-the-national-institutes-of-health-osteoarthritis-biomarkers-consortium
#15
JOURNAL ARTICLE
Shirley P Yu, Leticia A Deveza, Virginia B Kraus, Morten Karsdal, Anne-Christine Bay-Jensen, Jamie E Collins, Ali Guermazi, Frank W Roemer, Christoph Ladel, Venkatesha Bhagavath, David J Hunter
BACKGROUND: To assess the prognostic value of short-term change in biochemical markers as it relates to bone marrow lesions (BMLs) on MRI in knee osteoarthritis (OA) over 24 months and, furthermore, to assess the relationship between biochemical markers involved with tissue turnover and inflammation and BMLs on MRI. METHODS: Data from the Foundation for the National Institutes of Health OA Biomarkers Consortium within the Osteoarthritis Initiative (n = 600) was analyzed...
January 18, 2024: Arthritis Research & Therapy
https://read.qxmd.com/read/38232136/splicing-neoantigen-discovery-with-snaf-reveals-shared-targets-for-cancer-immunotherapy
#16
JOURNAL ARTICLE
Guangyuan Li, Shweta Mahajan, Siyuan Ma, Erin D Jeffery, Xuan Zhang, Anukana Bhattacharjee, Meenakshi Venkatasubramanian, Matthew T Weirauch, Emily R Miraldi, H Leighton Grimes, Gloria M Sheynkman, Tamara Tilburgs, Nathan Salomonis
Immunotherapy has emerged as a crucial strategy to combat cancer by "reprogramming" a patient's own immune system. Although immunotherapy is typically reserved for patients with a high mutational burden, neoantigens produced from posttranscriptional regulation may provide an untapped reservoir of common immunogenic targets for new targeted therapies. To comprehensively define tumor-specific and likely immunogenic neoantigens from patient RNA-Seq, we developed Splicing Neo Antigen Finder (SNAF), an easy-to-use and open-source computational workflow to predict splicing-derived immunogenic MHC-bound peptides (T cell antigen) and unannotated transmembrane proteins with altered extracellular epitopes (B cell antigen)...
January 17, 2024: Science Translational Medicine
https://read.qxmd.com/read/38207205/exploring-co-occurring-pole-exonuclease-and-non-exonuclease-domain-mutations-and-their-impact-on-tumor-mutagenicity
#17
JOURNAL ARTICLE
Shreya M Shah, Elena V Demidova, Salena Ringenbach, Bulat Faezov, Mark Andrake, Arjun Gandhi, Pilar Mur, Julen Viana-Errasti, Joanne Xiu, Jeffrey Swensen, Laura Valle, Roland L Dunbrack, Michael J Hall, Sanjeevani Arora
POLE driver mutations in the exonuclease domain (ExoD driver) are prevalent in several cancers, including colorectal cancer (CRC) and endometrial cancer (EC), leading to dramatically ultra-high tumor mutation burden (TMB). To understand whether POLE mutations that are not classified as drivers (POLE Variant) contribute to mutagenesis, we assessed TMB in 447 POLE-mutated CRCs, ECs, and ovarian cancers (OC) classified as TMB-High ≥10 mut/Mb (TMB-H) or TMB-Low <10 mut/Mb (TMB-L). TMB was significantly highest in tumors with 'POLE ExoD driver plus POLE Variant' (CRC and EC, p<0...
January 8, 2024: Cancer Res Commun
https://read.qxmd.com/read/38202027/blood-based-biomarkers-reflecting-protease-3-and-mmp-12-catalyzed-elastin-degradation-as-potential-noninvasive-surrogate-markers-of-endoscopic-and-clinical-disease-in-inflammatory-bowel-disease
#18
JOURNAL ARTICLE
Martin Pehrsson, Viktor Domislovic, Marta Sorokina Alexdottir, Marko Brinar, Morten Asser Karsdal, Ana Barisic, Zeljko Krznaric, Joachim Høg Mortensen
Chronic inflammation in inflammatory bowel disease (IBD) triggers significant extracellular matrix remodeling, including elastin remodeling, leading to severe clinical complications. Novel methods to assess intestinal tissue destruction may act as surrogate markers of endoscopic disease activity, relieving patients of invasive endoscopy. We explored the noninvasive blood-based biomarkers ELP-3 and ELM-12, measuring elastin degradation in IBD. In a study involving 104 Crohn's disease (CD), 39 ulcerative colitis (UC), and 29 healthy donors, we assessed these biomarkers' association with endoscopic and clinical disease activity using ELISA...
December 19, 2023: Journal of Clinical Medicine
https://read.qxmd.com/read/38189107/neoadjuvant-personalized-cancer-vaccines-the-final-frontier
#19
REVIEW
Guilhem Richard, Nicole Ruggiero, Gary D Steinberg, William D Martin, Anne S De Groot
INTRODUCTION: Clinical trials of personalized cancer vaccines have shown that on-demand therapies that are manufactured for each patient, result in activated T cell responses against individual tumor neoantigens. However, their use has been traditionally restricted to adjuvant settings and late-stage cancer therapy. There is growing support for the implementation of PCV earlier in the cancer therapy timeline, for reasons that will be discussed in this review. AREAS COVERED: The efficacy of cancer vaccines may be to some extent dependent on treatment(s) given prior to vaccine administration...
January 8, 2024: Expert Review of Vaccines
https://read.qxmd.com/read/38169963/understanding-islet-autoantibodies-in-prediction-of-type-1-diabetes
#20
REVIEW
Xiaofan Jia, Liping Yu
As screening studies and preventive interventions for type 1 diabetes (T1D) advance rapidly, the utility of islet autoantibodies (IAbs) in T1D prediction comes with challenges for early and accurate disease progression prediction. Refining features of IAbs can provide more accurate risk assessment. The advances in islet autoantibodies assay techniques help to screen out islet autoantibodies with high efficiency and high disease specificity. Exploring new islet autoantibodies to neoepitopes/neoantigens remains a hot research field for improving prediction and disease pathogenesis...
December 1, 2023: Journal of the Endocrine Society
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