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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
#62
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
#63
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
#64
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
#65
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
#66
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
#67
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
#68
COMMENT
Simona F Shaitelman, Wendy A Woodward
Neoadjuvant chemotherapy plus immunotherapy for triple-negative breast cancer (TNBC) is associated with improved but incomplete response. In this issue of Cancer Cell, Shiao et al. characterize longitudinal biopsies from a window of opportunity study with single-cell RNA sequencing (scRNA-seq) and spatial proteomic profiling and elucidate synergy between radiotherapy (RT) and pembrolizumab.
January 8, 2024: Cancer Cell
#69
LETTER
Elias Bou Farhat, Elio Adib, Melissa Daou, Abdul Rafeh Naqash, Ursula Matulonis, Kimmie Ng, David J Kwiatkowski, Lynette M Sholl, Amin H Nassar
Immunohistochemistry (IHC) is currently the first-line test for mismatch repair deficiency (MMR-D). Bou Farhat et al. show that mismatch repair (MMR) mutation signature by next-generation sequencing is a highly sensitive assay capable of detecting MMR-D cases that are missed in 1% and 5% of patients with MMR-D colorectal cancer (CRC) and endometrial cancer (EC), respectively. Patients with MMR-D tumors missed by IHC have similar clinical outcomes to patients with MMR-D by both IHC and mutation signature...
January 8, 2024: Cancer Cell
#70
JOURNAL ARTICLE
Vidhi Chandra, Le Li, Olivereen Le Roux, Yu Zhang, Rian M Howell, Dhwani N Rupani, Seyda Baydogan, Haiyan D Miller, Erick Riquelme, Joseph Petrosino, Michael P Kim, Krishna P L Bhat, James R White, Jay K Kolls, Yuliya Pylayeva-Gupta, Florencia McAllister
Microbes influence cancer initiation, progression and therapy responsiveness. IL-17 signaling contributes to gut barrier immunity by regulating microbes but also drives tumor growth. A knowledge gap remains regarding the influence of enteric IL-17-IL-17RA signaling and their microbial regulation on the behavior of distant tumors. We demonstrate that gut dysbiosis induced by systemic or gut epithelial deletion of IL-17RA induces growth of pancreatic and brain tumors due to excessive development of Th17, primary source of IL-17 in human and mouse pancreatic ductal adenocarcinoma, as well as B cells that circulate to distant tumors...
January 8, 2024: Cancer Cell
#71
REVIEW
Bertrand Routy, Tanisha Jackson, Laura Mählmann, Christina K Baumgartner, Martin Blaser, Allyson Byrd, Nathalie Corvaia, Kasey Couts, Diwakar Davar, Lisa Derosa, Howard C Hang, Geke Hospers, Morten Isaksen, Guido Kroemer, Florent Malard, Kathy D McCoy, Marlies Meisel, Sumanta Pal, Ze'ev Ronai, Eran Segal, Gregory D Sepich-Poore, Fyza Shaikh, Randy F Sweis, Giorgio Trinchieri, Marcel van den Brink, Rinse K Weersma, Katrine Whiteson, Liping Zhao, Jennifer McQuade, Hassane Zarour, Laurence Zitvogel
Over the last decade, the composition of the gut microbiota has been found to correlate with the outcomes of cancer patients treated with immunotherapy. Accumulating evidence points to the various mechanisms by which intestinal bacteria act on distal tumors and how to harness this complex ecosystem to circumvent primary resistance to immune checkpoint inhibitors. Here, we review the state of the microbiota field in the context of melanoma, the recent breakthroughs in defining microbial modes of action, and how to modulate the microbiota to enhance response to cancer immunotherapy...
January 8, 2024: Cancer Cell
#72
JOURNAL ARTICLE
Gianluca Mucciolo, Joaquín Araos Henríquez, Muntadher Jihad, Sara Pinto Teles, Judhell S Manansala, Wenlong Li, Sally Ashworth, Eloise G Lloyd, Priscilla S W Cheng, Weike Luo, Akanksha Anand, Ashley Sawle, Anna Piskorz, Giulia Biffi
Pancreatic ductal adenocarcinoma (PDAC) has a dismal prognosis. Cancer-associated fibroblasts (CAFs) are recognized potential therapeutic targets, but poor understanding of these heterogeneous cell populations has limited the development of effective treatment strategies. We previously identified transforming growth factor beta (TGF-β) as a main driver of myofibroblastic CAFs (myCAFs). Here, we show that epidermal growth factor receptor/Erb-B2 receptor (EGFR/ERBB2) signaling is induced by TGF-β in myCAFs through an autocrine process mediated by amphiregulin...
January 8, 2024: Cancer Cell
#73
JOURNAL ARTICLE
Sabina Kaczanowska, Tara Murty, Ahmad Alimadadi, Cristina F Contreras, Caroline Duault, Priyanka B Subrahmanyam, Warren Reynolds, Norma A Gutierrez, Reema Baskar, Catherine J Wu, Franziska Michor, Jennifer Altreuter, Yang Liu, Aashna Jhaveri, Vandon Duong, Hima Anbunathan, Claire Ong, Hua Zhang, Radim Moravec, Joyce Yu, Roshni Biswas, Stephen Van Nostrand, James Lindsay, Mina Pichavant, Elena Sotillo, Donna Bernstein, Amanda Carbonell, Joanne Derdak, Jacquelyn Klicka-Skeels, Julia E Segal, Eva Dombi, Stephanie A Harmon, Baris Turkbey, Bita Sahaf, Sean Bendall, Holden Maecker, Steven L Highfill, David Stroncek, John Glod, Melinda Merchant, Catherine C Hedrick, Crystal L Mackall, Sneha Ramakrishna, Rosandra N Kaplan
Chimeric antigen receptor T cells (CAR-Ts) have remarkable efficacy in liquid tumors, but limited responses in solid tumors. We conducted a Phase I trial (NCT02107963) of GD2 CAR-Ts (GD2-CAR.OX40.28.z.iC9), demonstrating feasibility and safety of administration in children and young adults with osteosarcoma and neuroblastoma. Since CAR-T efficacy requires adequate CAR-T expansion, patients were grouped into good or poor expanders across dose levels. Patient samples were evaluated by multi-dimensional proteomic, transcriptomic, and epigenetic analyses...
January 8, 2024: Cancer Cell
#74
JOURNAL ARTICLE
Yunfan Sun, Pin Wu, Zefan Zhang, Zejian Wang, Kaiqian Zhou, Minfang Song, Yuan Ji, Fenglin Zang, Limu Lou, Keqiang Rao, Pengxiang Wang, Yutong Gu, Jie Gu, Binbin Lu, Limeng Chen, Xiuqi Pan, Xiaojing Zhao, Lihua Peng, Dongbing Liu, Xiaofang Chen, Kui Wu, Penghui Lin, Liang Wu, Yulin Su, Min Du, Yingyong Hou, Xinrong Yang, Shuangjian Qiu, Yinghong Shi, Huichuan Sun, Jian Zhou, Xingxu Huang, David H Peng, Liye Zhang, Jia Fan
Comprehensive molecular analyses of metastatic hepatocellular carcinoma (HCC) are lacking. Here, we generate multi-omic profiling of 257 primary and 176 metastatic regions from 182 HCC patients. Primary tumors rich in hypoxia signatures facilitated polyclonal dissemination. Genomic divergence between primary and metastatic HCC is high, and early dissemination is prevalent. The remarkable neoantigen intratumor heterogeneity observed in metastases is associated with decreased T cell reactivity, resulting from disruptions to neoantigen presentation...
January 8, 2024: Cancer Cell
#75
JOURNAL ARTICLE
Amulya Sreekumar, Michelle Lu, Biswa Choudhury, Tien-Chi Pan, Dhruv K Pant, Matthew R Lawrence-Paul, Christopher J Sterner, George K Belka, Takashi Toriumi, Brian A Benz, Matias Escobar-Aguirre, Francesco E Marino, Jeffrey D Esko, Lewis A Chodosh
Breast cancer mortality results from incurable recurrences thought to be seeded by dormant, therapy-refractory residual tumor cells (RTCs). Understanding the mechanisms enabling RTC survival is therefore essential for improving patient outcomes. Here, we derive a dormancy-associated RTC signature that mirrors the transcriptional response to neoadjuvant therapy in patients and is enriched for extracellular matrix-related pathways. In vivo CRISPR-Cas9 screening of dormancy-associated candidate genes identifies the galactosyltransferase B3GALT6 as a functional regulator of RTC fitness...
January 8, 2024: Cancer Cell
#76
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
#77
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
#78
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
#79
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
#80
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
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