Review
Immunology
Julia Sbierski-Kind, Nicholas Mroz, Ari B. Molofsky
Summary: Perivascular niches are specialized microenvironments where stromal and immune cells interact with vasculature to monitor tissue status. Adventitial perivascular niches, particularly adventitial fibroblasts (AFs), play a significant role in regulating vascular integrity and supporting the activation of immune cells. Pericytes, on the other hand, support microvascular capillaries and organ-specific parenchymal cells in perivascular tissue immune niches.
IMMUNOLOGICAL REVIEWS
(2021)
Article
Oncology
Weiyu Ge, Ming Yue, Ruirong Lin, Tianhao Zhou, Haiyan Xu, Yu Wang, Tiebo Mao, Shumin Li, Xiuqi Wu, Xiaofei Zhang, Yongchao Wang, Jingyu Ma, Yanling Wang, Shengbai Xue, Daiyuan Shentu, Jiujie Cui, Liwei Wang
Summary: Our study identified a novel metabolic cancer associated fibroblasts subset (meCAFs) enriched in pancreatic ductal adenocarcinoma (PDAC) and related to CD8+ T cells accumulation. The abundance of meCAFs was associated with poor prognosis but better immunotherapy responses in PDAC patients. We demonstrated that PLA2G2A+ meCAFs impede the antitumor immune function of CD8+ T cells and facilitate tumor immune escape in PDAC.
Article
Cell Biology
Ioannis I. Verginadis, Harris Avgousti, James Monslow, Giorgos Skoufos, Frank Chinga, Kyle Kim, Nektaria Maria Leli, Ilias V. Karagounis, Brett I. Bell, Anastasia Velalopoulou, Carlo Salas Salinas, Victoria S. Wu, Yang Li, Jiangbin Ye, David A. Scott, Andrei L. Osterman, Arjun Sengupta, Aalim Weljie, Menggui Huang, Duo Zhang, Yi Fan, Enrico Radaelli, John W. Tobias, Florian Rambow, Panagiotis Karras, Jean-Christophe Marine, Xiaowei Xu, Artemis G. Hatzigeorgiou, Sandra Ryeom, J. Alan Diehl, Serge Y. Fuchs, Ellen Pure, Constantinos Koumenis
Summary: Bidirectional signalling between the tumour and stroma plays a crucial role in shaping tumour aggressiveness and metastasis. ATF4, a major effector of the Integrated Stress Response, regulates collagen biosynthesis and deposition in perivascular cancer-associated fibroblasts (CAFs), thereby supporting angiogenesis and progression in melanoma and pancreatic cancer.
NATURE CELL BIOLOGY
(2022)
Review
Immunology
Pei-Yu Chen, Wen-Fei Wei, Hong-Zhen Wu, Liang-Sheng Fan, Wei Wang
Summary: CAFs are important and heterogeneous components of the tumor extracellular matrix, with different origins and biomarkers, playing a role in immune regulation of the tumor microenvironment and exerting immunosuppressive functions through various mechanisms. Inhibition of CAFs and targeted therapy against CAFs offer new adjuvant means for immunotherapy.
FRONTIERS IN IMMUNOLOGY
(2021)
Review
Physiology
Giulia Biffi, David A. Tuveson
Summary: Efforts to develop anti-cancer therapies have mainly targeted the epithelial compartment, but recent studies have shown the significant influence of cancer-associated fibroblasts (CAFs) in tumor progression. CAFs not only promote cancer cell proliferation, therapy resistance, and immune exclusion, but may also restrain tumor progression in certain contexts. Research on CAFs has focused on their heterogeneity, plasticity, and functions across different cancer types and states, as well as advancements in therapeutic strategies targeting CAFs currently undergoing preclinical and clinical evaluation.
PHYSIOLOGICAL REVIEWS
(2021)
Article
Chemistry, Multidisciplinary
Mai T. Ngo, Jann N. Sarkaria, Brendan A. C. Harley
Summary: This article introduces a 3D in vitro model of the perivascular niche, which helps to understand the behavior and progression of brain tumor cells around blood vessels, and reveals the role of pericytes and astrocytes in regulating tumor cell invasion, proliferation, and therapeutic response.
Review
Oncology
Dor Lavie, Aviad Ben-Shmuel, Neta Erez, Ruth Scherz-Shouval
Summary: Cancer-associated fibroblasts (CAFs) play a central role in the microenvironment of solid tumors, and recent advances in single-cell technologies have provided insights into their complexity and heterogeneity. Understanding the subsets and functions of CAFs can potentially lead to better therapeutic strategies for cancer.
Article
Multidisciplinary Sciences
Rupsa Datta, Sharanya Sivanand, Allison N. Lau, Logan Florek, Anna M. Barbeau, Jeffrey Wyckoff, Melissa C. Skala, Matthew G. Vander Heiden
Summary: The direct interactions between pancreatic stellate cells (PSCs) and cancer cells promote a more oxidized state in cancer cells, overcoming the redox limitations of cell proliferation in pancreatic cancer.
Review
Biochemistry & Molecular Biology
Gregorie Lebeau, Franck Ah-Pine, Matthieu Daniel, Yosra Bedoui, Damien Vagner, Etienne Frumence, Philippe Gasque
Summary: Mesenchymal stem cells (MSCs) play a critical role in response to infection and can remove cell debris, regulate immune activities, control pathogens, and contribute to tissue remodeling. However, chronic infection and inflammation can affect the functions and immune regulatory activities of MSCs.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Multidisciplinary Sciences
Lee Shaashua, Aviad Ben-Shmuel, Meirav Pevsner-Fischer, Gil Friedman, Oshrat Levi-Galibov, Subhiksha Nandakumar, Debra Barki, Reinat Nevo, Lauren E. Brown, Wenhan Zhang, Yaniv Stein, Chen Lior, Han Sang Kim, Linda Bojmar, William R. Jarnagin, Nicolas Lecomte, Shimrit Mayer, Roni Stok, Hend Bishara, Rawand Hamodi, Ephrat Levy-Lahad, Talia Golan, John A. Porco, Christine A. Iacobuzio-Donahue, Nikolaus Schultz, David A. Tuveson, David Lyden, David Kelsen, Ruth Scherz-Shouval
Summary: Tumors are initiated by mutations in cancer cells and progress through interactions with non-malignant cells of the tumor microenvironment. This study examines how different mutations in cancer cells affect the transcriptional rewiring of cancer-associated fibroblasts (CAFs) in pancreatic cancer. The researchers find that BRCA mutations lead to an increase in a specific subset of immune-regulatory CAFs, mediated by activation of heat-shock factor 1.
NATURE COMMUNICATIONS
(2022)
Review
Neurosciences
F. Ah-Pine, M. Khettab, Y. Bedoui, Y. Slama, M. Daniel, B. Doray, P. Gasque
Summary: This review summarizes the potential roles of mesenchymal stromal cells in the context of glioblastoma and provides novel research avenues to better understand this lethal disease.
ACTA NEUROPATHOLOGICA COMMUNICATIONS
(2023)
Article
Cell Biology
Jingjing Qi, Adeline Crinier, Bertrand Escaliere, Youqiong Ye, Zhengting Wang, Tianyu Zhang, Luciana Batista, Hongzhi Liu, Liwen Hong, Ningbo Wu, Mingnan Zhang, Lei Chen, Yingbin Liu, Lei Shen, Emilie Narni-Mancinelli, Eric Vivier, Bing Su
Summary: Innate lymphoid cells (ILCs) are tissue-resident lymphocytes without antigen-specific receptors, and their roles in cancer immunity and immunotherapy are still unclear. Studies have identified tumor-specific ILC subsets in colorectal cancer (CRC) patients, with SLAMF1 potentially serving as an anti-tumor biomarker.
CELL REPORTS MEDICINE
(2021)
Review
Medicine, Research & Experimental
Dandan Gao, Liguang Fang, Cun Liu, Mengrui Yang, Xiaoyun Yu, Longyun Wang, Wenfeng Zhang, Changgang Sun, Jing Zhuang
Summary: The tumor microenvironment plays a crucial role in tumor cell proliferation, metastasis, and response to treatment. Cancer-associated fibroblasts (CAFs), the most abundant stromal cells, can alter the immunosuppressive effects of the microenvironment and influence immune cell function, allowing tumor cells to escape immune surveillance. This study provides a comprehensive review of fibroblast chemotaxis, malignant transformation, metabolic characteristics, and interactions with immune cells. It also summarizes current small molecule drugs that target CAFs, which have implications for improving the effectiveness of immunotherapy.
BIOMEDICINE & PHARMACOTHERAPY
(2023)
Article
Cell & Tissue Engineering
J. Lacy Kamm, Christopher B. Riley, Natalie A. Parlane, Erica K. Gee, C. Wayne Mcllwraith
Summary: The study found that MHC II-low MSCs are the most appropriate type of allogeneic MSC to prevent activation of the innate and cell-mediated component of the adaptive immune systems and have increased gene expression as compared to other allogeneic MSCs.
STEM CELL RESEARCH & THERAPY
(2021)
Review
Pharmacology & Pharmacy
Leon Jia Wei Tang, Ayshath Zaseela, Clarissa Chin Min Toh, Christabella Adine, Abdullah Omer Aydar, N. Gopalakrishna Iyer, Eliza Li Shan Fong
Summary: Advancements in single-cell technologies have increased our understanding of stromal heterogeneity, leading to the incorporation of this knowledge in tumor modeling for drug development and personalized drug testing. This approach may result in the development of more precise drugs targeting specific stromal cell subpopulations and improved recapitulation of patient tumors in vitro for personalized drug testing.
ADVANCED DRUG DELIVERY REVIEWS
(2021)
Article
Medicine, Research & Experimental
Christopher R. McEvoy, Holly Holliday, Niko Thio, Catherine Mitchell, David Y. Choong, Bhargavi Yellapu, Hui San Leong, Huiling Xu, Stephen Lade, Judy Browning, Elena A. Takano, David J. Byrne, Anthony J. Gill, Cuong P. Duong, Jason Li, Andrew P. Fellowes, Stephen B. Fox, Alexander Swarbrick, Owen W. J. Prall
Summary: This study describes a small round cell malignancy from the gastro-esophageal junction with a novel fusion between NUTM1 and MAD family member MXI1. In contrast to typical NUT carcinomas, this MXI1-NUTM1 tumor did not exhibit squamous differentiation and showed MYC-like characteristics without MYC expression. The findings suggest that MAD family members can be transformed into MYC-like mimics through fusion with NUTM1, indicating potential implications for diagnostic classification and therapeutic strategies for some NRN subtypes.
LABORATORY INVESTIGATION
(2021)
Article
Biochemistry & Molecular Biology
Theresa E. Hickey, Luke A. Selth, Kee Ming Chia, Geraldine Laven-Law, Heloisa H. Milioli, Daniel Roden, Shalini Jindal, Mun Hui, Jessica Finlay-Schultz, Esmaeil Ebrahimie, Stephen N. Birrell, Suzan Stelloo, Richard Iggo, Sarah Alexandrou, C. Elizabeth Caldon, Tarek M. Abdel-Fatah, Ian O. Ellis, Wilbert Zwart, Carlo Palmieri, Carol A. Sartorius, Alex Swarbrick, Elgene Lim, Jason S. Carroll, Wayne D. Tilley
Summary: Studies have shown that androgen receptor (AR) plays a tumor suppressor role in estrogen receptor (ER)-positive breast cancer, with AR activation helping to suppress cell cycle genes and promote the expression of tumor suppressor genes, enhancing therapeutic responses.
Article
Multidisciplinary Sciences
Holly Holliday, Daniel Roden, Simon Junankar, Sunny Z. Wu, Laura A. Baker, Christoph Krisp, Chia-Ling Chan, Andrea McFarland, Joanna N. Skhinas, Thomas R. Cox, Bhupinder Pal, Nicholas D. Huntington, Christopher J. Ormandy, Jason S. Carroll, Jane Visvader, Mark P. Molloy, Alexander Swarbrick
Summary: ID4 functions as a repressor of myoepithelial differentiation in mammary basal cells by regulating gene expression, antagonizing HEB transcriptional activity, and promoting appropriate tissue morphogenesis. During pregnancy, downregulation of ID4 modulates genes regulated by HEB, promoting specialization of basal cells into myoepithelial cells.
Article
Genetics & Heredity
Sunny Z. Wu, Daniel L. Roden, Ghamdan Al-Eryani, Nenad Bartonicek, Kate Harvey, Aurelie S. Cazet, Chia-Ling Chan, Simon Junankar, Mun N. Hui, Ewan A. Millar, Julia Beretov, Lisa Horvath, Anthony M. Joshua, Phillip Stricker, James S. Wilmott, Camelia Quek, Georgina Long, Richard A. Scolyer, Bertrand Z. Yeung, Davendra Segara, Cindy Mak, Sanjay Warrier, Joseph E. Powell, Sandra O'Toole, Elgene Lim, Alexander Swarbrick
Summary: The study demonstrates that viable cryopreservation of human cancers provides high-quality single cells for multi-omics analysis, preserving tumor heterogeneity while increasing correlations with freshly prepared cells for sequencing.
Article
Immunology
Kevin Mulder, Amit Ashok Patel, Wan Ting Kong, Cecile Piot, Evelyn Halitzki, Garett Dunsmore, Shabnam Khalilnezhad, Sergio Erdal Irac, Agathe Dubuisson, Marion Chevrier, Xiao Meng Zhang, John Kit Chung Tam, Tony Kiat Hon Lim, Regina Men Men Wong, Rhea Pai, Ahmed Ibrahim Samir Khalil, Pierce Kah Hoe Chow, Suny Z. Wu, Ghamdan Al-Eryani, Daniel Roden, Alexander Swarbrick, Jerry Kok Yen Chan, Salvatore Albani, Lisa Derosa, Laurence Zitvogel, Ankur Sharma, Jinmiao Chen, Aymeric Silvin, Antonio Bertoletti, Camille Bleriot, Charles-Antoine Dutertre, Florent Ginhoux
Summary: This study integrated a large number of mononuclear phagocytes from 13 tissues to generate a MNP single-cell RNA compendium, revealing conserved gene signatures and specialized cell subsets across multiple tissues. Specific macrophage populations were found to be expanded in cancer and inflammation, with tumor-associated macrophage populations present in all neoplastic tissues.
Meeting Abstract
Oncology
Louise A. Baldwin, Nenad Bartonicek, Jessica Yang, Sunny Z. Wu, Niantao Deng, Daniel Roden, Chia-Ling Chan, Ghamdan Al-Eryani, Damien J. Zanker, Belinda S. Parker, Alexander Swarbrick, Simon Junankar
Correction
Cell Biology
Sarah B. Crist, Travis Nemkov, Ruth F. Dumpit, Jinxiang Dai, Stephen J. Tapscott, Lawrence D. True, Alexander Swarbrick, Lucas B. Sullivan, Peter S. Nelson, Kirk C. Hansen, Cyrus M. Ghajar
NATURE CELL BIOLOGY
(2022)
Article
Cell Biology
Sarah B. Crist, Travis Nemkov, Ruth F. Dumpit, Jinxiang Dai, Stephen J. Tapscott, Lawrence D. True, Alexander Swarbrick, Lucas B. Sullivan, Peter S. Nelson, Kirk C. Hansen, Cyrus M. Ghajar
Summary: This study reveals that skeletal muscle imposes oxidative stress on disseminated tumour cells (DTCs), which inhibits their proliferation and prevents metastatic colonization. The findings suggest new vulnerabilities of DTCs that can be targeted to prevent metastasis in susceptible tissues.
NATURE CELL BIOLOGY
(2022)
Editorial Material
Genetics & Heredity
Daniel Roden, Alexander Swarbrick
Summary: A new study systematically characterizes the recurrent gene-expression programs controlling neoplastic cell states in various cancers using single-cell and spatial transcriptomics.
Article
Multidisciplinary Sciences
Michael Papanicolaou, Amelia L. Parker, Michelle Yam, Elysse C. Filipe, Sunny Z. Wu, Jessica L. Chitty, Kaitlin Wyllie, Emmi Tran, Ellie Mok, Audrey Nadalini, Joanna N. Skhinas, Morghan C. Lucas, David Herrmann, Max Nobis, Brooke A. Pereira, Andrew M. K. Law, Lesley Castillo, Kendelle J. Murphy, Anaiis Zaratzian, Jordan F. Hastings, David R. Croucher, Elgene Lim, Brian G. Oliver, Fatima Valdes Mora, Benjamin L. Parker, David Gallego-Ortega, Alexander Swarbrick, Sandra O'Toole, Paul Timpson, Thomas R. Cox
Summary: The distribution and organization of matrix molecules, particularly collagen I, in the tumor stroma play an important role in breast cancer progression. Cancer-associated fibroblasts (CAFs) remodel the extracellular matrix (ECM) to promote or inhibit tumor growth. It has been found that CAF-secreted collagen XII can alter the organization of collagen I, creating a pro-invasive microenvironment that supports metastatic dissemination. Collagen XII may serve as an indicator of breast cancer patients at high risk of metastatic relapse.
NATURE COMMUNICATIONS
(2022)
Editorial Material
Oncology
Ana C. Anderson, Itai Yanai, Lucy R. Yates, Linghua Wang, Alexander Swarbrick, Peter Sorger, Sandro Santagata, Wolf H. Fridman, Qiang Gao, Livnat Jerby, Benjamin Izar, Lulu Shang, Xiang Zhou
Article
Multidisciplinary Sciences
Louise A. Baldwin, Nenad Bartonicek, Jessica Yang, Sunny Z. Wu, Niantao Deng, Daniel L. Roden, Chia-Ling Chan, Ghamdan Al-Eryani, Damien J. Zanker, Belinda S. Parker, Alexander Swarbrick, Simon Junankar
Summary: Understanding the molecular mechanisms of cancer immunoediting and immune evasion at the clonal level is crucial for improving immunotherapeutic strategies. This study uses DNA barcoding to track the evolution of breast cancer cell clones during immunoediting and immunotherapy. The results reveal ongoing immunoediting during metastasis and treatment, as well as the presence of immune evasive clones with a gene signature associated with poor patient survival. The findings suggest that targeting specific genes in these clones could enhance immunotherapy response.
NATURE COMMUNICATIONS
(2022)
Article
Multidisciplinary Sciences
Khoa A. Tran, Venkateswar Addala, Rebecca L. Johnston, David Lovell, Andrew Bradley, Lambros T. Koufariotis, Scott Wood, Sunny Z. Wu, Daniel Roden, Ghamdan Al-Eryani, Alexander Swarbrick, Elizabeth D. Williams, John V. Pearson, Olga Kondrashova, Nicola Waddell
Summary: Cells in the tumour microenvironment (TME) can have a significant impact on tumour development and treatment response. Computational methods have been developed to analyze and separate TME from bulk RNA-seq data. In this study, the authors used single-cell RNA-seq data from breast cancer to generate simulated bulk data and compared the performance of nine different TME deconvolution methods. They found that some methods were more effective in deconvolving mixtures with high tumour purity levels, while most methods tended to misclassify normal epithelial cells as cancer epithelial cells as tumour purity increased. The authors also discovered that the molecular subtype of breast cancer played a role in this misclassification. BayesPrism and DWLS had the lowest number of false positives and false negatives, making them the most reliable methods for deconvolving specific immune lineages. These findings emphasize the importance of characterizing rare cell types using single-cell techniques and taking into account the tumour cell composition when deconvolving the TME.
NATURE COMMUNICATIONS
(2023)
Article
Oncology
Niantao Deng, Andre Minoche, Kate Harvey, Meng Li, Juliane Winkler, Andrei Goga, Alex Swarbrick
Summary: In this study, deep whole genome sequencing was conducted on commonly used breast cancer cell lines and patient-derived xenograft models, leading to the identification of novel genomic alterations and features. This provides a comprehensive genome sequencing resource for these models.
BREAST CANCER RESEARCH
(2022)