journal
https://read.qxmd.com/read/38039965/a-road-map-for-the-treatment-of-pediatric-diffuse-midline-glioma
#81
JOURNAL ARTICLE
Carl Koschmann, Wajd N Al-Holou, Marta M Alonso, Jamie Anastas, Pratiti Bandopadhayay, Tara Barron, Oren Becher, Rodrigo Cartaxo, Maria G Castro, Chan Chung, Madison Clausen, Derek Dang, Robert Doherty, Ryan Duchatel, Matthew Dun, Mariella Filbin, Andrea Franson, Stefanie Galban, Marc Garcia Moure, Hugh Garton, Pruthvi Gowda, Joana Graca Marques, Cynthia Hawkins, Allison Heath, Esther Hulleman, Sunjong Ji, Chris Jones, Lindsay Kilburn, Cassie Kline, Michael A Koldobskiy, Daniel Lim, Pedro R Lowenstein, Q Richard Lu, Joanna Lum, Stephen Mack, Suresh Magge, Bernard Marini, Donna Martin, Neena Marupudi, Dana Messinger, Rajen Mody, Meredith Morgan, Mateus Mota, Karin Muraszko, Sabine Mueller, Siva Kumar Natarajan, Javad Nazarian, Michael Niculcea, Nicholas Nuechterlein, Hideho Okada, Valerie Opipari, Manjunath P Pai, Sharmistha Pal, Erik Peterson, Timothy Phoenix, John R Prensner, Matthew Pun, G Praveen Raju, Zachary J Reitman, Adam Resnick, David Rogawski, Amanda Saratsis, Stefanie G Sbergio, Mark Souweidane, James M Stafford, Theophilos Tzaridis, Sujatha Venkataraman, Orazio Vittorio, Jack Wadden, Daniel Wahl, Robert J Wechsler-Reya, Viveka Nand Yadav, Xu Zhang, Qiang Zhang, Sriram Venneti
Recent clinical trials for H3K27-altered diffuse midline gliomas (DMGs) have shown much promise. We present a consensus roadmap and identify three major barriers: (1) refinement of experimental models to include immune and brain-specific components; (2) collaboration among researchers, clinicians, and industry to integrate patient-derived data through sharing, transparency, and regulatory considerations; and (3) streamlining clinical efforts including biopsy, CNS-drug delivery, endpoint determination, and response monitoring...
January 8, 2024: Cancer Cell
https://read.qxmd.com/read/38134937/gd2-car-car-t%C3%A2-cells-in-patients-with-osteosarcoma-and-neuroblastoma-it-s-not-only-the-t-cells-that-matter
#82
JOURNAL ARTICLE
Azlann B Arnett, Andras Heczey
GD2-CAR T cells were safe and anti-tumor responses were limited. In this issue of Cancer Cell, Kaczanowska et al. find that apheresis products and peripheral blood at baseline contained significantly higher proportions of CXCR3+ monocytes in good expanders. CXCR3+ monocytes may influence CAR T cell function.
December 16, 2023: Cancer Cell
https://read.qxmd.com/read/38086335/druggable-growth-dependencies-and-tumor-evolution-analysis-in-patient-derived-organoids-of-neuroendocrine-neoplasms-from-multiple-body-sites
#83
JOURNAL ARTICLE
Talya L Dayton, Nicolas Alcala, Laura Moonen, Lisanne den Hartigh, Veerle Geurts, Lise Mangiante, Lisa Lap, Antonella F M Dost, Joep Beumer, Sonja Levy, Rachel S van Leeuwaarde, Wenzel M Hackeng, Kris Samsom, Catherine Voegele, Alexandra Sexton-Oates, Harry Begthel, Jeroen Korving, Lisa Hillen, Lodewijk A A Brosens, Sylvie Lantuejoul, Sridevi Jaksani, Niels F M Kok, Koen J Hartemink, Houke M Klomp, Inne H M Borel Rinkes, Anne-Marie Dingemans, Gerlof D Valk, Menno R Vriens, Wieneke Buikhuisen, José van den Berg, Margot Tesselaar, Jules Derks, Ernst Jan Speel, Matthieu Foll, Lynnette Fernández-Cuesta, Hans Clevers
Neuroendocrine neoplasms (NENs) comprise well-differentiated neuroendocrine tumors (NETs) and poorly differentiated neuroendocrine carcinomas (NECs). Treatment options for patients with NENs are limited, in part due to lack of accurate models. We establish patient-derived tumor organoids (PDTOs) from pulmonary NETs and derive PDTOs from an understudied subtype of NEC, large cell neuroendocrine carcinoma (LCNEC), arising from multiple body sites. PDTOs maintain the gene expression patterns, intra-tumoral heterogeneity, and evolutionary processes of parental tumors...
December 11, 2023: Cancer Cell
https://read.qxmd.com/read/38086334/alkemy-to-enhance-chimeric-antigen-receptor-t%C3%A2-cell-immunotherapy-for-neuroblastoma
#84
JOURNAL ARTICLE
Marco Ruella
Chimeric antigen receptor (CAR) T cell immunotherapy in solid cancer is severely limited by the absence of ideal targets. In this issue of Cancer Cell, Bergaggio et al. find that anaplastic lymphoma kinase (ALK) inhibitors can enhance the function of ALK-specific CAR T cells against neuroblastoma by increasing target density in cancer cells.
December 11, 2023: Cancer Cell
https://read.qxmd.com/read/38086333/nen-in-a-dish-a-patient-derived-organoid-biobank-illuminates-potential-novel-therapeutic-opportunities-for-neuroendocrine-neoplasms
#85
JOURNAL ARTICLE
Stefanie Gerstberger, Karuna Ganesh
Neuroendocrine neoplasms are rare cancers with limited treatment options and preclinical models. In this issue of Cancer Cell, Dayton et al. establish a patient-derived tumor organoid biobank encompassing pulmonary low-grade neuroendocrine tumors (LNETs) and high-grade neuroendocrine carcinomas (LCNECs), identifying novel biomarker-dependent therapeutic vulnerabilities using niche perturbation and drug response assays.
December 11, 2023: Cancer Cell
https://read.qxmd.com/read/38039964/alk-inhibitors-increase-alk-expression-and-sensitize-neuroblastoma-cells-to-alk-car-t-cells
#86
JOURNAL ARTICLE
Elisa Bergaggio, Wei-Tien Tai, Andrea Aroldi, Carmen Mecca, Elisa Landoni, Manuel Nüesch, Ines Mota, Jasna Metovic, Luca Molinaro, Leyuan Ma, Diego Alvarado, Chiara Ambrogio, Claudia Voena, Rafael B Blasco, Tongqing Li, Daryl Klein, Darrell J Irvine, Mauro Papotti, Barbara Savoldo, Gianpietro Dotti, Roberto Chiarle
Selection of the best tumor antigen is critical for the therapeutic success of chimeric antigen receptor (CAR) T cells in hematologic malignancies and solid tumors. The anaplastic lymphoma kinase (ALK) receptor is expressed by most neuroblastomas while virtually absent in most normal tissues. ALK is an oncogenic driver in neuroblastoma and ALK inhibitors show promising clinical activity. Here, we describe the development of ALK.CAR-T cells that show potent efficacy in monotherapy against neuroblastoma with high ALK expression without toxicity...
December 11, 2023: Cancer Cell
https://read.qxmd.com/read/38039963/phenotypic-signatures-of-circulating-neoantigen-reactive-cd8-t%C3%A2-cells-in-patients-with-metastatic-cancers
#87
JOURNAL ARTICLE
Rami Yossef, Sri Krishna, Sivasish Sindiri, Frank J Lowery, Amy R Copeland, Jared J Gartner, Maria R Parkhurst, Neilesh B Parikh, Kyle J Hitscherich, Shoshana T Levi, Praveen D Chatani, Nikolaos Zacharakis, Noam Levin, Nolan R Vale, Shirley K Nah, Aaron Dinerman, Victoria K Hill, Satyajit Ray, Alakesh Bera, Lior Levy, Li Jia, Michael C Kelly, Stephanie L Goff, Paul F Robbins, Steven A Rosenberg
Circulating T cells from peripheral blood (PBL) can provide a rich and noninvasive source for antitumor T cells. By single-cell transcriptomic profiling of 36 neoantigen-specific T cell clones from 6 metastatic cancer patients, we report the transcriptional and cell surface signatures of antitumor PBL-derived CD8+ T cells (NeoTCRPBL ). Comparison of tumor-infiltrating lymphocyte (TIL)- and PBL-neoantigen-specific T cells revealed that NeoTCRPBL T cells are low in frequency and display less-dysfunctional memory phenotypes relative to their TIL counterparts...
December 11, 2023: Cancer Cell
https://read.qxmd.com/read/38039962/genomic-alterations-driving-precancerous-to-cancerous-lesions-in-esophageal-cancer-development
#88
JOURNAL ARTICLE
Jiang Chang, Xuan Zhao, Yichen Wang, Tianyuan Liu, Ce Zhong, Yueqiong Lao, Shaosen Zhang, Han Liao, Fan Bai, Dongxin Lin, Chen Wu
Esophageal squamous cell carcinoma (ESCC) develops through a series of increasingly abnormal precancerous lesions. Previous studies have revealed the striking differences between normal esophageal epithelium and ESCC in copy number alterations (CNAs) and mutations in genes driving clonal expansion. However, due to limited data on early precancerous lesions, the timing of these transitions and which among them are prerequisites for malignant transformation remained unclear. Here, we analyze 1,275 micro-biopsies from normal esophagus, early and late precancerous lesions, and esophageal cancers to decipher the genomic alterations at each stage...
December 11, 2023: Cancer Cell
https://read.qxmd.com/read/37995682/therapeutic-targeting-of-ep300-cbp-by-bromodomain-inhibition-in-hematologic-malignancies
#89
JOURNAL ARTICLE
Luciano Nicosia, Gary J Spencer, Nigel Brooks, Fabio M R Amaral, Naseer J Basma, John A Chadwick, Bradley Revell, Bettina Wingelhofer, Alba Maiques-Diaz, Oliver Sinclair, Francesco Camera, Filippo Ciceri, Daniel H Wiseman, Neil Pegg, Will West, Tomasz Knurowski, Kris Frese, Karen Clegg, Victoria L Campbell, James Cavet, Mhairi Copland, Emma Searle, Tim C P Somervaille
CCS1477 (inobrodib) is a potent, selective EP300/CBP bromodomain inhibitor which induces cell-cycle arrest and differentiation in hematologic malignancy model systems. In myeloid leukemia cells, it promotes rapid eviction of EP300/CBP from an enhancer subset marked by strong MYB occupancy and high H3K27 acetylation, with downregulation of the subordinate oncogenic network and redistribution to sites close to differentiation genes. In myeloma cells, CCS1477 induces eviction of EP300/CBP from FGFR3, the target of the common (4; 14) translocation, with redistribution away from IRF4-occupied sites to TCF3/E2A-occupied sites...
December 11, 2023: Cancer Cell
https://read.qxmd.com/read/37977148/a-longitudinal-single-cell-atlas-of-treatment-response-in-pediatric-aml
#90
JOURNAL ARTICLE
Sander Lambo, Diane L Trinh, Rhonda E Ries, Dan Jin, Audi Setiadi, Michelle Ng, Veronique G Leblanc, Michael R Loken, Lisa E Brodersen, Fangyan Dai, Laura M Pardo, Xiaotu Ma, Suzanne M Vercauteren, Soheil Meshinchi, Marco A Marra
Pediatric acute myeloid leukemia (pAML) is characterized by heterogeneous cellular composition, driver alterations and prognosis. Characterization of this heterogeneity and how it affects treatment response remains understudied in pediatric patients. We used single-cell RNA sequencing and single-cell ATAC sequencing to profile 28 patients representing different pAML subtypes at diagnosis, remission and relapse. At diagnosis, cellular composition differed between genetic subgroups. Upon relapse, cellular hierarchies transitioned toward a more primitive state regardless of subtype...
December 11, 2023: Cancer Cell
https://read.qxmd.com/read/37977147/the-antitumor-activities-of-anti-cd47-antibodies-require-fc-fc%C3%AE-r-interactions
#91
JOURNAL ARTICLE
Juan C Osorio, Patrick Smith, David A Knorr, Jeffrey V Ravetch
While anti-CD47 antibodies hold promise for cancer immunotherapy, early-phase clinical trials have shown limited clinical benefit, suggesting that CD47 blockade alone might be insufficient for effective tumor control. Here, we investigate the contributions of the Fc domain of anti-CD47 antibodies required for optimal in vivo antitumor activity across multiple species-matched models, providing insights into the mechanisms behind the efficacy of this emerging class of therapeutic antibodies. Using a mouse model humanized for CD47, SIRPα, and FcγRs, we demonstrate that local administration of Fc-engineered anti-CD47 antibodies with enhanced binding to activating FcγRs promotes tumor infiltration of macrophages and antigen-specific T cells, while depleting regulatory T cells...
December 11, 2023: Cancer Cell
https://read.qxmd.com/read/37890491/from-intestinal-metaplasia-to-gastric-cancer-witnessing-the-rise-of-evil-over-time-and-space
#92
JOURNAL ARTICLE
Cheng Zhang, Xi Jiao, Lin Shen
Intestinal metaplasia (IM) is a precancerous lesion associated with increased gastric cancer (GC) risk. However, the molecular characteristics and heterogeneity distinguishing the two stages remain unclear. Huang et al. provide a spatiotemporal insight into the transition from IM to GC, offering the potential for tailored precision prevention strategies for GC.
December 11, 2023: Cancer Cell
https://read.qxmd.com/read/37890490/bringing-car-t%C3%A2-cell-therapy-trials-to-underserved-populations
#93
JOURNAL ARTICLE
Hoda Badr, Rayne Rouce, Michael E Scheurer, Premal Lulla, Martha Mims, Pavan Reddy
There is a critical need for equitable access to cell therapies in cancer treatment, particularly within public safety-net healthcare systems that serve minority and socioeconomically disadvantaged populations. We discuss how the Dan L Duncan Comprehensive Cancer Center at Baylor College of Medicine is piloting a cell therapy program aimed at addressing cancer care disparities and has the potential to serve as a national model for enhancing health equity in cancer care.
December 11, 2023: Cancer Cell
https://read.qxmd.com/read/37995683/temporal-evolution-reveals-bifurcated-lineages-in-aggressive-neuroendocrine-small-cell-prostate-cancer-trans-differentiation
#94
JOURNAL ARTICLE
Chia-Chun Chen, Wendy Tran, Kai Song, Tyler Sugimoto, Matthew B Obusan, Liang Wang, Katherine M Sheu, Donghui Cheng, Lisa Ta, Grigor Varuzhanyan, Arthur Huang, Runzhe Xu, Yuanhong Zeng, Amirreza Borujerdpur, Nicholas A Bayley, Miyako Noguchi, Zhiyuan Mao, Colm Morrissey, Eva Corey, Peter S Nelson, Yue Zhao, Jiaoti Huang, Jung Wook Park, Owen N Witte, Thomas G Graeber
Trans-differentiation from an adenocarcinoma to a small cell neuroendocrine state is associated with therapy resistance in multiple cancer types. To gain insight into the underlying molecular events of the trans-differentiation, we perform a multi-omics time course analysis of a pan-small cell neuroendocrine cancer model (termed PARCB), a forward genetic transformation using human prostate basal cells and identify a shared developmental, arc-like, and entropy-high trajectory among all transformation model replicates...
November 16, 2023: Cancer Cell
https://read.qxmd.com/read/37922910/anti-pd-1-immunotherapy-with-androgen-deprivation-therapy-induces-robust-immune-infiltration-in-metastatic-castration-sensitive-prostate-cancer
#95
JOURNAL ARTICLE
Jessica E Hawley, Aleksandar Z Obradovic, Matthew C Dallos, Emerson A Lim, Karie Runcie, Casey R Ager, James McKiernan, Christopher B Anderson, Guarionex J Decastro, Joshua Weintraub, Renu Virk, Israel Lowy, Jianhua Hu, Matthew G Chaimowitz, Xinzheng V Guo, Ya Zhang, Michael C Haffner, Jeremy Worley, Mark N Stein, Andrea Califano, Charles G Drake
When compared to other malignancies, the tumor microenvironment (TME) of primary and castration-resistant prostate cancer (CRPC) is relatively devoid of immune infiltrates. While androgen deprivation therapy (ADT) induces a complex immune infiltrate in localized prostate cancer, the composition of the TME in metastatic castration-sensitive prostate cancer (mCSPC), and the effects of ADT and other treatments in this context are poorly understood. Here, we perform a comprehensive single-cell RNA sequencing (scRNA-seq) profiling of metastatic sites from patients participating in a phase 2 clinical trial (NCT03951831) that evaluated standard-of-care chemo-hormonal therapy combined with anti-PD-1 immunotherapy...
November 13, 2023: Cancer Cell
https://read.qxmd.com/read/37890494/mitochondrial-control-of-antigen-presentation-in-cancer-cells
#96
COMMENT
Ruth Soler-Agesta, Alberto Anel, Lorenzo Galluzzi
Cytotoxic T lymphocytes recognize and kill cancer cells when the latter present antigenic epitopes complexed with MHC class I molecules on their surface. In a recent Science paper, Mangalhara et al. show that alterations of the mitochondrial electron flow upregulate multiple factors involved in antigen presentation via a succinate-dependent epigenetic mechanism.
November 13, 2023: Cancer Cell
https://read.qxmd.com/read/37890492/tumor-sequencing-of-african-ancestry-reveals-differences-in-clinically-relevant-alterations-across-common-cancers
#97
JOURNAL ARTICLE
Evelyn Jiagge, Dexter X Jin, Justin Y Newberg, Tomin Perea-Chamblee, Kelly R Pekala, Christopher Fong, Michele Waters, David Ma, Yvonne Dei-Adomakoh, Gilles Erb, Kanika S Arora, Sophia L Maund, Njoki Njiraini, Atara Ntekim, Susie Kim, Xuechun Bai, Marlene Thomas, Ronwyn van Eeden, Priti Hegde, Justin Jee, Debyani Chakravarty, Nikolaus Schultz, Michael F Berger, Garrett M Frampton, Ethan S Sokol, Jian Carrot-Zhang
Cancer genomes from patients with African (AFR) ancestry have been poorly studied in clinical research. We leverage two large genomic cohorts to investigate the relationship between genomic alterations and AFR ancestry in six common cancers. Cross-cancer type associations, such as an enrichment of MYC amplification with AFR ancestry in lung, breast, and prostate cancers, and depletion of BRAF alterations are observed in colorectal and pancreatic cancers. There are differences in actionable alterations, such as depletion of KRAS G12C and EGFR L858R, and enrichment of ROS1 fusion with AFR ancestry in lung cancers...
November 13, 2023: Cancer Cell
https://read.qxmd.com/read/37863068/in%C3%A2-vivo-macrophage-engineering-reshapes-the-tumor-microenvironment-leading-to-eradication-of-liver-metastases
#98
JOURNAL ARTICLE
Thomas Kerzel, Giovanna Giacca, Stefano Beretta, Chiara Bresesti, Marco Notaro, Giulia Maria Scotti, Chiara Balestrieri, Tamara Canu, Miriam Redegalli, Federica Pedica, Marco Genua, Renato Ostuni, Anna Kajaste-Rudnitski, Masanobu Oshima, Giovanni Tonon, Ivan Merelli, Luca Aldrighetti, Paolo Dellabona, Nadia Coltella, Claudio Doglioni, Paola M V Rancoita, Francesca Sanvito, Luigi Naldini, Mario Leonardo Squadrito
Liver metastases are associated with poor response to current pharmacological treatments, including immunotherapy. We describe a lentiviral vector (LV) platform to selectively engineer liver macrophages, including Kupffer cells and tumor-associated macrophages (TAMs), to deliver type I interferon (IFNα) to liver metastases. Gene-based IFNα delivery delays the growth of colorectal and pancreatic ductal adenocarcinoma liver metastases in mice. Response to IFNα is associated with TAM immune activation, enhanced MHC-II-restricted antigen presentation and reduced exhaustion of CD8+ T cells...
November 13, 2023: Cancer Cell
https://read.qxmd.com/read/37863067/the-one-two-punch-tim-3-blockade-targets-immune-and-tumor-cells-to-knock-out-pediatric-brain-tumors
#99
COMMENT
Juyeun Lee, Justin D Lathia
Diffuse midline gliomas (DMGs) pose treatment challenges due to their location within the brainstem and invasive nature. Although classical immune checkpoint inhibitors have demonstrated limited success in clinical trials, Ausejo-Mauleon et al. demonstrate TIM-3 is an effective DMG strategy, targeting both immune and tumor cells for dual therapeutic benefit.
November 13, 2023: Cancer Cell
https://read.qxmd.com/read/37863066/tumor-resident-lactobacillus-iners-confer-chemoradiation-resistance-through-lactate-induced-metabolic-rewiring
#100
JOURNAL ARTICLE
Lauren E Colbert, Molly B El Alam, Rui Wang, Tatiana Karpinets, David Lo, Erica J Lynn, Timothy A Harris, Jacob H Elnaggar, Kyoko Yoshida-Court, Katarina Tomasic, Julianna K Bronk, Julie Sammouri, Ananta V Yanamandra, Adilene V Olvera, Lily G Carlin, Travis Sims, Andrea Y Delgado Medrano, Tatiana Cisneros Napravnik, Madison O'Hara, Daniel Lin, Chike O Abana, Hannah X Li, Patricia J Eifel, Anuja Jhingran, Melissa Joyner, Lilie Lin, Lois M Ramondetta, Andrew M Futreal, Kathleen M Schmeler, Geena Mathew, Stephanie Dorta-Estremera, Jianhua Zhang, Xiaogang Wu, Nadim J Ajami, Matthew Wong, Cullen Taniguchi, Joseph F Petrosino, K Jagannadha Sastry, Pablo C Okhuysen, Sara A Martinez, Lin Tan, Iqbal Mahmud, Philip L Lorenzi, Jennifer A Wargo, Ann H Klopp
Tumor microbiota can produce active metabolites that affect cancer and immune cell signaling, metabolism, and proliferation. Here, we explore tumor and gut microbiome features that affect chemoradiation response in patients with cervical cancer using a combined approach of deep microbiome sequencing, targeted bacterial culture, and in vitro assays. We identify that an obligate L-lactate-producing lactic acid bacterium found in tumors, Lactobacillus iners, is associated with decreased survival in patients, induces chemotherapy and radiation resistance in cervical cancer cells, and leads to metabolic rewiring, or alterations in multiple metabolic pathways, in tumors...
November 13, 2023: Cancer Cell
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