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Elias Bou Farhat, Elio Adib, Melissa Daou, Abdul Rafeh Naqash, Ursula Matulonis, Kimmie Ng, David J Kwiatkowski, Lynette M Sholl, Amin H Nassar
No abstract text is available yet for this article.
February 12, 2024: Cancer Cell
#42
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
No abstract text is available yet for this article.
February 12, 2024: Cancer Cell
#43
Michael S Samuel, Jose I Lopez, Ewan J McGhee, Daniel R Croft, David Strachan, Paul Timpson, June Munro, Ewald Schröder, Jing Zhou, Valerie G Brunton, Nick Barker, Hans Clevers, Owen J Sansom, Kurt I Anderson, Valerie M Weaver, Michael F Olson
No abstract text is available yet for this article.
February 12, 2024: Cancer Cell
#44
REVIEW
Xupeng Yang, Chen Yang, Shu Zhang, Haigang Geng, Andrew X Zhu, René Bernards, Wenxin Qin, Jia Fan, Cun Wang, Qiang Gao
The past decade has witnessed significant advances in the systemic treatment of advanced hepatocellular carcinoma (HCC). Nevertheless, the newly developed treatment strategies have not achieved universal success and HCC patients frequently exhibit therapeutic resistance to these therapies. Precision treatment represents a paradigm shift in cancer treatment in recent years. This approach utilizes the unique molecular characteristics of individual patient to personalize treatment modalities, aiming to maximize therapeutic efficacy while minimizing side effects...
February 12, 2024: Cancer Cell
#45
COMMENT
Y A DeClerck
Exploring the diversity within the tumor microenvironment (TME) can offer crucial insights to steer cancer therapy toward precision medicine. In this issue of Cancer Cell, Wienke et al. undertake a comprehensive single-cell analysis of neuroblastoma, unveiling its immune landscape and identifying NECTIN2-TIGIT as a promising target for immunotherapy.
February 12, 2024: Cancer Cell
#46
COMMENT
Derek De-Rui Huang, James Chih-Hsin Yang
Immune checkpoint inhibitors have reshaped the treatment landscape of non-small cell lung cancer (NSCLC). However, chemoimmunotherapy trials dedicated to squamous NSCLC are limited. In this issue of Cancer Cell, Zhou et al. demonstrate serplulimab plus chemotherapy as an effective first-line regimen to treat patients with advanced squamous NSCLC.
February 12, 2024: Cancer Cell
#47
JOURNAL ARTICLE
Dorota D Klysz, Carley Fowler, Meena Malipatlolla, Lucille Stuani, Katherine A Freitas, Yiyun Chen, Stefanie Meier, Bence Daniel, Katalin Sandor, Peng Xu, Jing Huang, Louai Labanieh, Vimal Keerthi, Amaury Leruste, Malek Bashti, Janette Mata-Alcazar, Nikolaos Gkitsas, Justin A Guerrero, Chris Fisher, Sunny Patel, Kyle Asano, Shabnum Patel, Kara L Davis, Ansuman T Satpathy, Steven A Feldman, Elena Sotillo, Crystal L Mackall
Adenosine (Ado) mediates immune suppression in the tumor microenvironment and exhausted CD8+ CAR-T cells express CD39 and CD73, which mediate proximal steps in Ado generation. Here, we sought to enhance CAR-T cell potency by knocking out CD39, CD73, or adenosine receptor 2a (A2aR) but observed only modest effects. In contrast, overexpression of Ado deaminase (ADA-OE), which metabolizes Ado to inosine (INO), induced stemness and enhanced CAR-T functionality. Similarly, CAR-T cell exposure to INO augmented function and induced features of stemness...
February 12, 2024: Cancer Cell
#48
JOURNAL ARTICLE
Simon Heeke, Carl M Gay, Marcos R Estecio, Hai Tran, Benjamin B Morris, Bingnan Zhang, Ximing Tang, Maria Gabriela Raso, Pedro Rocha, Siqi Lai, Edurne Arriola, Paul Hofman, Veronique Hofman, Prasad Kopparapu, Christine M Lovly, Kyle Concannon, Luana Guimaraes De Sousa, Whitney Elisabeth Lewis, Kimie Kondo, Xin Hu, Azusa Tanimoto, Natalie I Vokes, Monique B Nilsson, Allison Stewart, Maarten Jansen, Ildikó Horváth, Mina Gaga, Vasileios Panagoulias, Yael Raviv, Danny Frumkin, Adam Wasserstrom, Aharona Shuali, Catherine A Schnabel, Yuanxin Xi, Lixia Diao, Qi Wang, Jianjun Zhang, Peter Van Loo, Jing Wang, Ignacio I Wistuba, Lauren A Byers, John V Heymach
Small cell lung cancer (SCLC) is an aggressive malignancy composed of distinct transcriptional subtypes, but implementing subtyping in the clinic has remained challenging, particularly due to limited tissue availability. Given the known epigenetic regulation of critical SCLC transcriptional programs, we hypothesized that subtype-specific patterns of DNA methylation could be detected in tumor or blood from SCLC patients. Using genomic-wide reduced-representation bisulfite sequencing (RRBS) in two cohorts totaling 179 SCLC patients and using machine learning approaches, we report a highly accurate DNA methylation-based classifier (SCLC-DMC) that can distinguish SCLC subtypes...
February 12, 2024: Cancer Cell
#49
COMMENT
Xingying Zhang, Haoyi Wang
Adenosine (Ado) drives immune suppression in the tumor microenvironment. In this issue of Cancer Cell, Klysz et al. investigate Ado-mediated immunosuppression. Overexpression of Ado deaminase (ADA-OE), metabolizing Ado to inosine (INO), induces stemness and improves CAR T cell functionality. Likewise, exposure to INO enhances CAR T cells' function and induces stemness features.
February 12, 2024: Cancer Cell
#50
JOURNAL ARTICLE
Clare Pacini, Emma Duncan, Emanuel Gonçalves, James Gilbert, Shriram Bhosle, Stuart Horswell, Emre Karakoc, Howard Lightfoot, Ed Curry, Francesc Muyas, Monsif Bouaboula, Chandra Sekhar Pedamallu, Isidro Cortes-Ciriano, Fiona M Behan, Lykourgos-Panagiotis Zalmas, Andrew Barthorpe, Hayley Francies, Steve Rowley, Jack Pollard, Pedro Beltrao, Leopold Parts, Francesco Iorio, Mathew J Garnett
Genetic screens in cancer cell lines inform gene function and drug discovery. More comprehensive screen datasets with multi-omics data are needed to enhance opportunities to functionally map genetic vulnerabilities. Here, we construct a second-generation map of cancer dependencies by annotating 930 cancer cell lines with multi-omic data and analyze relationships between molecular markers and cancer dependencies derived from CRISPR-Cas9 screens. We identify dependency-associated gene expression markers beyond driver genes, and observe many gene addiction relationships driven by gain of function rather than synthetic lethal effects...
February 12, 2024: Cancer Cell
#51
JOURNAL ARTICLE
James D Phelan, Sebastian Scheich, Jaewoo Choi, George W Wright, Björn Häupl, Ryan M Young, Sara A Rieke, Martine Pape, Yanlong Ji, Henning Urlaub, Arnold Bolomsky, Carmen Doebele, Alena Zindel, Tanja Wotapek, Monica Kasbekar, Brett Collinge, Da Wei Huang, Zana A Coulibaly, Vivian M Morris, Xiaoxuan Zhuang, Julius C Enssle, Xin Yu, Weihong Xu, Yandan Yang, Hong Zhao, Zhuo Wang, Andy D Tran, Christopher J Shoemaker, Galina Shevchenko, Daniel J Hodson, Arthur L Shaffer, Louis M Staudt, Thomas Oellerich
Diffuse large B cell lymphoma (DLBCL) is an aggressive, profoundly heterogeneous cancer, presenting a challenge for precision medicine. Bruton's tyrosine kinase (BTK) inhibitors block B cell receptor (BCR) signaling and are particularly effective in certain molecular subtypes of DLBCL that rely on chronic active BCR signaling to promote oncogenic NF-κB. The MCD genetic subtype, which often acquires mutations in the BCR subunit, CD79B, and in the innate immune adapter, MYD88L265P , typically resists chemotherapy but responds exceptionally to BTK inhibitors...
February 12, 2024: Cancer Cell
#52
JOURNAL ARTICLE
Danish Memon, Adam J Schoenfeld, Darwin Ye, George Fromm, Hira Rizvi, Xiang Zhang, Mohamed Reda Keddar, Divij Mathew, Kyung Jin Yoo, Jingya Qiu, Jayon Lihm, Jayalaksmi Miriyala, Jennifer L Sauter, Jia Luo, Andrew Chow, Umesh K Bhanot, Caroline McCarthy, Chad M Vanderbilt, Cailian Liu, Mohsen Abu-Akeel, Andrew J Plodkowski, Nicholas McGranahan, Marta Łuksza, Benjamin D Greenbaum, Taha Merghoub, Ikbel Achour, J Carl Barrett, Ross Stewart, Pedro Beltrao, Taylor H Schreiber, Andy J Minn, Martin L Miller, Matthew D Hellmann
Although immunotherapy with PD-(L)1 blockade is routine for lung cancer, little is known about acquired resistance. Among 1,201 patients with non-small cell lung cancer (NSCLC) treated with PD-(L)1 blockade, acquired resistance is common, occurring in >60% of initial responders. Acquired resistance shows differential expression of inflammation and interferon (IFN) signaling. Relapsed tumors can be separated by upregulated or stable expression of IFNγ response genes. Upregulation of IFNγ response genes is associated with putative routes of resistance characterized by signatures of persistent IFN signaling, immune dysfunction, and mutations in antigen presentation genes which can be recapitulated in multiple murine models of acquired resistance to PD-(L)1 blockade after in vitro IFNγ treatment...
February 12, 2024: Cancer Cell
#53
JOURNAL ARTICLE
Madeleine Benguigui, Tim J Cooper, Prajakta Kalkar, Sagie Schif-Zuck, Ruth Halaban, Antonella Bacchiocchi, Iris Kamer, Abhilash Deo, Bar Manobla, Rotem Menachem, Jozafina Haj-Shomaly, Avital Vorontsova, Ziv Raviv, Chen Buxbaum, Petros Christopoulos, Jair Bar, Michal Lotem, Mario Sznol, Amiram Ariel, Shai S Shen-Orr, Yuval Shaked
Despite the remarkable success of anti-cancer immunotherapy, its effectiveness remains confined to a subset of patients-emphasizing the importance of predictive biomarkers in clinical decision-making and further mechanistic understanding of treatment response. Current biomarkers, however, lack the power required to accurately stratify patients. Here, we identify interferon-stimulated, Ly6Ehi neutrophils as a blood-borne biomarker of anti-PD1 response in mice at baseline. Ly6Ehi neutrophils are induced by tumor-intrinsic activation of the STING (stimulator of interferon genes) signaling pathway and possess the ability to directly sensitize otherwise non-responsive tumors to anti-PD1 therapy, in part through IL12b-dependent activation of cytotoxic T cells...
February 12, 2024: Cancer Cell
#54
JOURNAL ARTICLE
Judith Wienke, Lindy L Visser, Waleed M Kholosy, Kaylee M Keller, Marta Barisa, Evon Poon, Sophie Munnings-Tomes, Courtney Himsworth, Elizabeth Calton, Ana Rodriguez, Ronald Bernardi, Femke van den Ham, Sander R van Hooff, Yvette A H Matser, Michelle L Tas, Karin P S Langenberg, Philip Lijnzaad, Anne L Borst, Elisa Zappa, Francisca J Bergsma, Josephine G M Strijker, Bronte M Verhoeven, Shenglin Mei, Amira Kramdi, Restuadi Restuadi, Alvaro Sanchez-Bernabeu, Annelisa M Cornel, Frank C P Holstege, Juliet C Gray, Godelieve A M Tytgat, Marijn A Scheijde-Vermeulen, Marc H W A Wijnen, Miranda P Dierselhuis, Karin Straathof, Sam Behjati, Wei Wu, Albert J R Heck, Jan Koster, Stefan Nierkens, Isabelle Janoueix-Lerosey, Ronald R de Krijger, Ninib Baryawno, Louis Chesler, John Anderson, Hubert N Caron, Thanasis Margaritis, Max M van Noesel, Jan J Molenaar
Pediatric patients with high-risk neuroblastoma have poor survival rates and urgently need more effective treatment options with less side effects. Since novel and improved immunotherapies may fill this need, we dissect the immunoregulatory interactions in neuroblastoma by single-cell RNA-sequencing of 24 tumors (10 pre- and 14 post-chemotherapy, including 5 pairs) to identify strategies for optimizing immunotherapy efficacy. Neuroblastomas are infiltrated by natural killer (NK), T and B cells, and immunosuppressive myeloid populations...
February 12, 2024: Cancer Cell
#55
LETTER
Jessica A Lavery, Paul C Boutros, Daniel Knight, Tuomas Tammela, Chaya S Moskowitz, Lee W Jones
Lavery et al. show that the association between exercise and risk of cancer varied as a function of organ site and amount of exercise. Exercise was also associated with a longevity benefit regardless of a cancer diagnosis or not. This study further highlights the importance of exercise as an effective cancer preventive strategy.
February 12, 2024: Cancer Cell
#56
JOURNAL ARTICLE
Caicun Zhou, Yanping Hu, Ekaterine Arkania, Saadettin Kilickap, Kejing Ying, Fei Xu, Lin Wu, Xiang Wang, Maksym Viguro, Tamta Makharadze, Hongmei Sun, Feng Luo, Jianhua Shi, Aimin Zang, Yueyin Pan, Zhendong Chen, Zhongyao Jia, Vladimer Kuchava, Ping Lu, Ling Zhang, Ying Cheng, Wenying Kang, Qingyu Wang, Haoyu Yu, Jing Li, Jun Zhu
Combining immunotherapy with chemotherapy can provide improved survival in advanced squamous non-small-cell lung cancer (NSCLC) patients without targetable gene alterations. 537 previously untreated patients with stage IIIB/IIIC or IV squamous NSCLC without targetable gene alterations were enrolled and randomized (2:1) to receive serplulimab 4.5 mg/kg or placebo, both in combination with nab-paclitaxel and carboplatin, intravenously in 3-week cycles. The primary endpoint of progression-free survival (PFS) was met at the first interim analysis...
February 12, 2024: Cancer Cell
#57
JOURNAL ARTICLE
Stephen L Shiao, Kenneth H Gouin, Nathan Ing, Alice Ho, Reva Basho, Aagam Shah, Richard H Mebane, David Zitser, Andrew Martinez, Natalie-Ya Mevises, Bassem Ben-Cheikh, Regina Henson, Monica Mita, Philomena McAndrew, Scott Karlan, Armando Giuliano, Alice Chung, Farin Amersi, Catherine Dang, Heather Richardson, Wonwoo Shon, Farnaz Dadmanesh, Michele Burnison, Amin Mirhadi, Zachary S Zumsteg, Rachel Choi, Madison Davis, Joseph Lee, Dustin Rollins, Cynthia Martin, Negin H Khameneh, Heather McArthur, Simon R V Knott
Strategies are needed to better identify patients that will benefit from immunotherapy alone or who may require additional therapies like chemotherapy or radiotherapy to overcome resistance. Here we employ single-cell transcriptomics and spatial proteomics to profile triple negative breast cancer biopsies taken at baseline, after one cycle of pembrolizumab, and after a second cycle of pembrolizumab given with radiotherapy. Non-responders lack immune infiltrate before and after therapy and exhibit minimal therapy-induced immune changes...
January 8, 2024: Cancer Cell
#58
JOURNAL ARTICLE
Mirjam E Hoekstra, Maarten Slagter, Jos Urbanus, Mireille Toebes, Nadine Slingerland, Iris de Rink, Roelof J C Kluin, Marja Nieuwland, Ron Kerkhoven, Lodewyk F A Wessels, Ton N Schumacher
Cells in the tumor microenvironment (TME) influence each other through secretion and sensing of soluble mediators, such as cytokines and chemokines. While signaling of interferon γ (IFNγ) and tumor necrosis factor α (TNFα) is integral to anti-tumor immune responses, our understanding of the spatiotemporal behavior of these cytokines is limited. Here, we describe a single cell transcriptome-based approach to infer which signal(s) an individual cell has received. We demonstrate that, contrary to expectations, CD8+ T cell-derived IFNγ is the dominant modifier of the TME relative to TNFα...
January 8, 2024: Cancer Cell
#59
JOURNAL ARTICLE
Anna Adam-Artigues, Luis E Valencia Salazar, Julio A Aguirre-Ghiso
Rare disseminated tumor cells (DTCs) can persist after treatment in patients for years, and the immune system does not eliminate them. Goddard et al. propose that immune evasion by rare dormant DTCs is due to an improbability of contact imposed by large distances separating effector T cells and DTCs.
January 8, 2024: Cancer Cell
#60
JOURNAL ARTICLE
Erica T Goddard, Miles H Linde, Shivani Srivastava, Grant Klug, Tamer B Shabaneh, Santino Iannone, Candice A Grzelak, Sydney Marsh, Alessandra I Riggio, Ryann E Shor, Ian L Linde, Marissa Guerrero, Joshua R Veatch, Annelise G Snyder, Alana L Welm, Stanley R Riddell, Cyrus M Ghajar
The period between "successful" treatment of localized breast cancer and the onset of distant metastasis can last many years, representing an unexploited window to eradicate disseminated disease and prevent metastases. We find that the source of recurrence-disseminated tumor cells (DTCs) -evade endogenous immunity directed against tumor neoantigens. Although DTCs downregulate major histocompatibility complex I, this does not preclude recognition by conventional T cells. Instead, the scarcity of interactions between two relatively rare populations-DTCs and endogenous antigen-specific T cells-underlies DTC persistence...
January 8, 2024: Cancer Cell
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