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JOURNAL ARTICLE
Mu-Chen Zhang, Shuang Tian, Di Fu, Li Wang, Shu Cheng, Hong-Mei Yi, Xu-Feng Jiang, Qi Song, Yan Zhao, Yang He, Jian-Feng Li, Rong-Ji Mu, Hai Fang, Hao Yu, Hui Xiong, Biao Li, Sai-Juan Chen, Peng-Peng Xu, Wei-Li Zhao
We report the results of GUIDANCE-01 (NCT04025593), a randomized, phase II trial of R-CHOP alone or combined with targeted agents (R-CHOP-X) guided by genetic subtyping of newly diagnosed, intermediate-risk, or high-risk diffuse large B cell lymphoma (DLBCL). A total of 128 patients were randomized 1:1 to receive R-CHOP-X or R-CHOP. The study achieved the primary endpoint, showing significantly higher complete response rate with R-CHOP-X than R-CHOP (88% vs. 66%, p = 0.003), with overall response rate of 92% vs...
September 18, 2023: Cancer Cell
#22
JOURNAL ARTICLE
Cynthia K Hahn, Adam C Palmer, David M Weinstock
Zhang et al. report a randomized phase 2 trial for diffuse large B cell lymphoma (DLBCL) that compared standard of care (R-CHOP) to R-CHOP combined with one of 5 agents matched to an individual lymphoma's genetics. Overall, the matching strategy significantly outperformed R-CHOP, laying the foundation for a paradigm-shifting phase 3 trial.
September 15, 2023: Cancer Cell
#23
LETTER
Xubin Li, Jared Henderson, Max J Gordon, Irtiza Sheikh, Loretta J Nastoupil, Jason Westin, Christopher Flowers, Sairah Ahmed, Linghua Wang, Sattva S Neelapu, Paolo Strati, Qing Deng, Michael R Green
Li et al. present a resource of single-cell RNA sequencing (scRNA-seq) data from the infusion products of relapsed or refractory large B cell lymphoma (rrLBCL) patients treated with standard-of-care axicabtagene ciloleucel and identify features that are significantly different between products from responders and non-responders at 3-month followup by PET/CT, an important landmark for long-term outcomes.
September 15, 2023: Cancer Cell
#24
JOURNAL ARTICLE
Qi Cai, Sarah Warren, Violena Pietrobon, Markus Maeurer, Lei S Qi, Timothy K Lu, Marc J Lajoie, David Barrett, David F Stroncek, Francesco M Marincola
Successful implementation of adoptive cell therapy (ACT) of cancer requires comprehensively addressing biological and practical challenges. This approach has been largely overlooked, resulting in a gap between the potential of ACT and its actual effectiveness. We summarize the most promising technical strategies in creating an "ideal" ACT product, focusing on chimeric antigen receptor (CAR)-engineered cells. Since many requirements for effective ACT are common to most cancers, what we outline here might have a broader impact...
September 13, 2023: Cancer Cell
#25
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
#26
JOURNAL ARTICLE
Ning-Ning Liu, Cheng-Xiang Yi, Lu-Qi Wei, Jin-An Zhou, Tong Jiang, Cong-Cong Hu, Lu Wang, Yuan-Yuan Wang, Yun Zou, Yi-Kai Zhao, Le-Le Zhang, Ya-Ting Nie, Yi-Jing Zhu, Xin-Yao Yi, Ling-Bing Zeng, Jing-Quan Li, Xiao-Tian Huang, Hong-Bin Ji, Zisis Kozlakidis, Lin Zhong, Christopher Heeschen, Xiao-Qi Zheng, Changbin Chen, Peng Zhang, Hui Wang
Although polymorphic microbiomes have emerged as hallmarks of cancer, far less is known about the role of the intratumor mycobiome as living microorganisms in cancer progression. Here, using fungi-enriched DNA extraction and deep shotgun metagenomic sequencing, we have identified enriched tumor-resident Aspergillus sydowii in patients with lung adenocarcinoma (LUAD). By three different syngeneic lung cancer mice models, we find that A. sydowii promotes lung tumor progression via IL-1β-mediated expansion and activation of MDSCs, resulting in suppressed activity of cytotoxic T lymphocyte cells and accumulation of PD-1+ CD8+ T cells...
November 13, 2023: Cancer Cell
#27
JOURNAL ARTICLE
Hongyi Zhang, Xuexin Yu, Jianfeng Ye, Huiyu Li, Jing Hu, Yuhao Tan, Yan Fang, Esra Akbay, Fulong Yu, Chen Weng, Vijay G Sankaran, Robert M Bachoo, Elizabeth Maher, John Minna, Anli Zhang, Bo Li
Mitochondria (MT) participate in most metabolic activities of mammalian cells. A near-unidirectional mitochondrial transfer from T cells to cancer cells was recently observed to "metabolically empower" cancer cells while "depleting immune cells," providing new insights into tumor-T cell interaction and immune evasion. Here, we leverage single-cell RNA-seq technology and introduce MERCI, a statistical deconvolution method for tracing and quantifying mitochondrial trafficking between cancer and T cells...
October 9, 2023: Cancer Cell
#28
JOURNAL ARTICLE
Yi Pan, Jia-Tao Zhang, Xuan Gao, Zhi-Yong Chen, Bingfa Yan, Pei-Xin Tan, Xiao-Rong Yang, Wei Gao, Yuhua Gong, Zihan Tian, Si-Yang Maggie Liu, Hui Lin, Hao Sun, Jie Huang, Si-Yang Liu, Hong-Hong Yan, Song Dong, Chong-Rui Xu, Hua-Jun Chen, Zhen Wang, Pansong Li, Yanfang Guan, Bin-Chao Wang, Jin-Ji Yang, Hai-Yan Tu, Xue-Ning Yang, Wen-Zhao Zhong, Xuefeng Xia, Xin Yi, Qing Zhou, Yi-Long Wu
The value of circulating tumor DNA (ctDNA) during chemoradiotherapy (CRT) remains unclear but is critical for detecting molecular residual disease (MRD). In this prospective study, we sequenced 761 blood samples from 139 patients with locally advanced non-small cell lung cancer treated with definitive radiation therapy (RT). ctDNA concentrations showed a significantly declining trend as CRT progressed at on-RT and after-RT time points versus baseline. Thirty-eight (27.3%) patients with early undetectable ctDNA at both on-RT (RT reached 40 Gy) and after-RT time points, indicating early response to CRT, had better survival outcomes for both with or without consolidation immune checkpoint inhibitors...
October 9, 2023: Cancer Cell
#29
COMMENT
Ziming Li, Shun Lu
In this issue of Cancer Cell, Chen et al. and Pan et al. employ personalized, tumor-informed technology to detect minimal residual disease in non-small-cell lung cancer and demonstrate the clinical promise of integrating liquid biopsy techniques to improve the assessment of cancer progression and metastasis risk.
October 9, 2023: Cancer Cell
#30
JOURNAL ARTICLE
Donjeta Gjuka, Elio Adib, Kendra Garrison, Jianfeng Chen, Yuxue Zhang, Wenjiao Li, Daniel Boutz, Candice Lamb, Yuri Tanno, Amin Nassar, Talal El Zarif, Neil Kale, Mehrdad Rakaee, Tarek H Mouhieddine, Sarah Abou Alaiwi, Alexander Gusev, Thomas Rogers, Jianjun Gao, George Georgiou, David J Kwiatkowski, Everett Stone
Chromosomal region 9p21 containing tumor suppressors CDKN2A/B and methylthioadenosine phosphorylase (MTAP) is one of the most frequent genetic deletions in cancer. 9p21 loss is correlated with reduced tumor-infiltrating lymphocytes (TILs) and resistance to immune checkpoint inhibitor (ICI) therapy. Previously thought to be caused by CDKN2A/B loss, we now show that it is loss of MTAP that leads to poor outcomes on ICI therapy and reduced TIL density. MTAP loss causes accumulation of methylthioadenosine (MTA) both intracellularly and extracellularly and profoundly impairs T cell function via the inhibition of protein arginine methyltransferase 5 (PRMT5) and by adenosine receptor agonism...
October 9, 2023: Cancer Cell
#31
JOURNAL ARTICLE
Mingrui Zhu, Jiwoong Kim, Qing Deng, Biagio Ricciuti, Joao V Alessi, Buse Eglenen-Polat, Matthew E Bender, Hai-Cheng Huang, Ryan R Kowash, Ileana Cuevas, Zachary T Bennett, Jinming Gao, John D Minna, Diego H Castrillon, Mark M Awad, Lin Xu, Esra A Akbay
The role of tumor mutational burden (TMB) in shaping tumor immunity is a key question that has not been addressable using genetically engineered mouse models (GEMMs) of lung cancer. To induce TMB in lung GEMMs, we expressed an ultra-mutator variant of DNA polymerase-E (POLE)P286R in lung epithelial cells. Introduction of PoleP286R allele into KrasG12D and KrasG12D ; p53L/L (KP) models significantly increase their TMB. Immunogenicity and sensitivity to immune checkpoint blockade (ICB) induced by Pole is partially dependent on p53...
October 9, 2023: Cancer Cell
#32
JOURNAL ARTICLE
Valentina Ferrari, Antonino Lo Cascio, Alessia Melacarne, Nina Tanasković, Alessandro M Mozzarelli, Luca Tiraboschi, Michela Lizier, Marta Salvi, Daniele Braga, Francesca Algieri, Giuseppe Penna, Maria Rescigno
Recent data have shown that gut microbiota has a major impact on the clinical response to immune checkpoint inhibitors (ICIs) in the context of solid tumors. ICI-based therapy acts by unlocking cognate cytotoxic T lymphocyte (CTL) effector responses, and increased sensitivity to ICIs is due to an enhancement of patients' tumor antigen (TA)-specific CTL responses. Cancer clearance by TA-specific CTL requires expression of relevant TAs on cancer cells' HLA class I molecules, and reduced HLA class I expression is a common mechanism used by cancer cells to evade the immune system...
October 9, 2023: Cancer Cell
#33
JOURNAL ARTICLE
Erin M Parry, Camilla K Lemvigh, Stephanie Deng, Nathan Dangle, Neil Ruthen, Binyamin A Knisbacher, Julien Broséus, Sébastien Hergalant, Romain Guièze, Shuqiang Li, Wandi Zhang, Connor Johnson, Jaclyn M Long, Shanye Yin, Lillian Werner, Annabelle Anandappa, Noelia Purroy, Satyen Gohil, Giacomo Oliveira, Pavan Bachireddy, Sachet A Shukla, Teddy Huang, Joseph D Khoury, Beenu Thakral, Michael Dickinson, Constantine Tam, Kenneth J Livak, Gad Getz, Donna Neuberg, Pierre Feugier, Peter Kharchenko, William Wierda, Lars Rønn Olsen, Nitin Jain, Catherine J Wu
Unlike many other hematologic malignancies, Richter syndrome (RS), an aggressive B cell lymphoma originating from indolent chronic lymphocytic leukemia, is responsive to PD-1 blockade. To discover the determinants of response, we analyze single-cell transcriptome data generated from 17 bone marrow samples longitudinally collected from 6 patients with RS. Response is associated with intermediate exhausted CD8 effector/effector memory T cells marked by high expression of the transcription factor ZNF683, determined to be evolving from stem-like memory cells and divergent from terminally exhausted cells...
October 9, 2023: Cancer Cell
#34
JOURNAL ARTICLE
Hirohito Yamaguchi, Mien-Chie Hung
The CD58-CD2 axis regulates T cell-mediated cancer immunity, but little is known about the regulation of CD58. In two recent papers pubished in Cancer Cell, Miao et al. and Ho et al. define a mechanism of CD58 regulation by CMTM6 and show an unexpected yin-yang link between PD-L1 and CD58.
October 9, 2023: Cancer Cell
#35
JOURNAL ARTICLE
Brian G Topp, Madhav Channavazzala, Kapil Mayawala, Dinesh P De Alwis, Eric Rubin, Alexandra Snyder, Jedd D Wolchok, Antoni Ribas
While many patients are treated beyond progression (TBP), the magnitude and duration of clinical benefit in these patients have not been fully quantified. Data from 799 patients with melanoma (n = 176), non-small cell lung cancer (NSCLC; n = 146), gastric cancer (GC; n = 87), head and neck squamous cell carcinoma (HNSCC; n = 112), clear-cell renal cell carcinoma (ccRCC; n = 51), and urothelial carcinoma (UC; n = 227) TBP were included. Patients had received pembrolizumab beyond confirmed progressive disease (PD) per RECIST v1...
September 11, 2023: Cancer Cell
#36
COMMENT
Erica S Tsang, Lillian L Siu
In this issue of Cancer Cell, Topp et al. analyze data from 799 patients treated with pembrolizumab beyond progression by RECIST 1.1 across six trials. Although 8.9%-24.4% of patients demonstrate a ≥30% reduction in target lesions, conversely 11%-18% of patients had a ≥20% increase. The benefits of treatment beyond progression must be carefully weighed against physical and financial toxicities.
September 11, 2023: Cancer Cell
#37
JOURNAL ARTICLE
Zsolt Megyesfalvi, Simon Heeke, Benjamin J Drapkin, Anna Solta, Ildiko Kovacs, Kristiina Boettiger, Lilla Horvath, Busra Ernhofer, Janos Fillinger, Ferenc Renyi-Vamos, Clemens Aigner, Karin Schelch, Christian Lang, Gyorgy Marko-Varga, Carl M Gay, Lauren A Byers, Benjamin B Morris, John V Heymach, Peter Van Loo, Fred R Hirsch, Balazs Dome
The understanding of small cell lung cancer (SCLC) biology has increased dramatically in recent years, but the processes that allow SCLC to progress rapidly remain poorly understood. Here, we advocate the integration of rapid autopsies and preclinical models into SCLC research as a comprehensive strategy with the potential to revolutionize current treatment paradigms.
September 11, 2023: Cancer Cell
#38
JOURNAL ARTICLE
Alberto Sanchez-Aguilera, Mariam Masmudi-Martín, Andrea Navas-Olive, Patricia Baena, Carolina Hernández-Oliver, Neibla Priego, Lluís Cordón-Barris, Laura Alvaro-Espinosa, Santiago García, Sonia Martínez, Miguel Lafarga, Michael Z Lin, Fátima Al-Shahrour, Liset Menendez de la Prida, Manuel Valiente
A high percentage of patients with brain metastases frequently develop neurocognitive symptoms; however, understanding how brain metastasis co-opts the function of neuronal circuits beyond a tumor mass effect remains unknown. We report a comprehensive multidimensional modeling of brain functional analyses in the context of brain metastasis. By testing different preclinical models of brain metastasis from various primary sources and oncogenic profiles, we dissociated the heterogeneous impact on local field potential oscillatory activity from cortical and hippocampal areas that we detected from the homogeneous inter-model tumor size or glial response...
September 11, 2023: Cancer Cell
#39
MULTICENTER STUDY
Sophia J Wagner, Daniel Reisenbüchler, Nicholas P West, Jan Moritz Niehues, Jiefu Zhu, Sebastian Foersch, Gregory Patrick Veldhuizen, Philip Quirke, Heike I Grabsch, Piet A van den Brandt, Gordon G A Hutchins, Susan D Richman, Tanwei Yuan, Rupert Langer, Josien C A Jenniskens, Kelly Offermans, Wolfram Mueller, Richard Gray, Stephen B Gruber, Joel K Greenson, Gad Rennert, Joseph D Bonner, Daniel Schmolze, Jitendra Jonnagaddala, Nicholas J Hawkins, Robyn L Ward, Dion Morton, Matthew Seymour, Laura Magill, Marta Nowak, Jennifer Hay, Viktor H Koelzer, David N Church, Christian Matek, Carol Geppert, Chaolong Peng, Cheng Zhi, Xiaoming Ouyang, Jacqueline A James, Maurice B Loughrey, Manuel Salto-Tellez, Hermann Brenner, Michael Hoffmeister, Daniel Truhn, Julia A Schnabel, Melanie Boxberg, Tingying Peng, Jakob Nikolas Kather
Deep learning (DL) can accelerate the prediction of prognostic biomarkers from routine pathology slides in colorectal cancer (CRC). However, current approaches rely on convolutional neural networks (CNNs) and have mostly been validated on small patient cohorts. Here, we develop a new transformer-based pipeline for end-to-end biomarker prediction from pathology slides by combining a pre-trained transformer encoder with a transformer network for patch aggregation. Our transformer-based approach substantially improves the performance, generalizability, data efficiency, and interpretability as compared with current state-of-the-art algorithms...
September 11, 2023: Cancer Cell
#40
COMMENT
Pekka Ruusuvuori, Mira Valkonen, Leena Latonen
Artificial intelligence (AI) is rapidly gaining interest in medicine, including pathological assessments for personalized medicine. In this issue of Cancer Cell, Wagner et al. demonstrate superior accuracy of transformer-based deep learning in predicting biomarker status in CRC. The work has implications for increased efficiency and accuracy in clinical diagnostics guiding treatment decisions in precision oncology.
September 11, 2023: Cancer Cell
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