Review
Cell Biology
Mrinmoy Sarkar, Tristan Nguyen, Esheksha Gundre, Olajumoke Ogunlusi, Mohanad El-Sobky, Biplab Giri, Tapasree Roy Sarkar
Summary: Stromal heterogeneity of tumor microenvironment (TME) is crucial for malignancy and therapeutic resistance. Cancer-associated fibroblasts (CAFs) play a significant role in the tumor stroma, posing challenges to current therapies for breast cancer and other types of cancer. The positive feedback loop between CAFs and cancer cells contributes to the establishment of malignancy and reduces the efficacy of anti-cancer treatments. Understanding CAF-induced therapeutic resistance is important for improving cancer therapy outcomes.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2023)
Review
Oncology
Geraldine Gentric, Fatima Mechta-Grigoriou
Summary: Tumors exhibit metabolic heterogeneity with utilization of carbon sources other than glucose, such as amino acids, fatty acids, and lactate. This diversity in metabolic pathways influences cancer cell invasion capabilities and is also present in Cancer-Associated Fibroblasts (CAF).
Review
Cell Biology
Ester Pfeifer, Joy M. Burchell, Francesco Dazzi, Debashis Sarker, Richard Beatson
Summary: PDAC is associated with poor prognosis due to advanced stage at diagnosis and aggressive tumor biology. Efforts to target CAF, a predominant cell type in the tumor microenvironment, have shown disappointing results in clinical trials.
Article
Oncology
Meng Zhang, Junlong Zhu, Pan Zhang, Lingxun Li, Min Min, Tinghao Li, Weiyang He
Summary: Bladder cancer is a common and highly morbid cancer of the genitourinary system. Cancer-associated fibroblasts (CAFs) play a critical role in the development of bladder cancer. In this study, we identified five genes associated with CAFs and constructed a prognostic model for bladder cancer.
FRONTIERS IN ONCOLOGY
(2023)
Review
Pharmacology & Pharmacy
Chunxue Zhang, Yuxiang Fei, Hui Wang, Sheng Hu, Chao Liu, Rong Hu, Qianming Du
Summary: Cancer immunotherapy has opened up a new frontier in cancer treatment, but the lack of specificity and resistance to targeted therapies have hindered their effectiveness. Recent research has focused on the role of cancer-associated fibroblasts (CAFs) in immune regulation and their impact on tumor progression. CAFs interact with immune cells to create a tumor immune microenvironment (TIME) that promotes malignant tumor progression, thereby contributing to the failure of cancer immunotherapies. This review highlights the immunosuppressive function of CAFs, the mechanisms of CAFs-immune cell interactions, and discusses potential CAF-targeted therapeutic strategies for future investigation.
FRONTIERS IN PHARMACOLOGY
(2023)
Article
Medicine, Research & Experimental
Xuechun Li, Zhao Sun, Gongxin Peng, Yi Xiao, Junchao Guo, Bin Wu, Xiaoyi Li, Weixun Zhou, Jiarui Li, Zhe Li, Chunmei Bai, Lin Zhao, Qin Han, Robert Chunhua Zhao, Xiaoyue Wang
Summary: This study reveals the characteristics of different CAF subsets in gastric cancer (GC) and their interactions with the tumor microenvironment (TME) using single-cell RNA sequencing and multistaining registration techniques. The results demonstrate that iCAFs and eCAFs not only exhibit enhanced protumor activities, but also mobilize surrounding immune cells to construct a tumor-favorable microenvironment.
Article
Biochemistry & Molecular Biology
Federica Papaccio, Daniela Kovacs, Barbara Bellei, Silvia Caputo, Emilia Migliano, Carlo Cota, Mauro Picardo
Summary: Research indicates that cancer-associated fibroblasts play significant roles in tumor growth, extracellular matrix remodeling, and inflammatory response. A thorough understanding of the melanoma-fibroblast relationship can expand treatment options.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Oncology
Sabrina Rizzolio, Silvia Giordano, Simona Corso
Summary: In the last two decades, targeted drugs have revolutionized clinical oncology. However, primary and acquired resistance to these therapies has become a significant limitation, with cancer-associated fibroblasts (CAFs) playing a crucial role. CAFs not only contribute to tumor stroma structure, but also release various molecules that impact tumor properties, including response to drug treatment. The role of CAFs in resistance to targeted therapies, particularly molecular therapies, has been overlooked.
JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH
(2022)
Article
Medicine, Research & Experimental
Ambre Giguelay, Evgenia Turtoi, Lakhdar Khelaf, Guillaume Tosato, Ikrame Dadi, Tommy Chastel, Marie-Alix Poul, Marine Pratlong, Stefan Nicolescu, Dany Severac, Antoine Adenis, Olivia Sgarbura-Popescu, Sebastien Carrere, Philippe Rouanet, Marc Ychou, Francois Quenet, Didier Pourqier, Pierre-Emmanuel Colombo, Andrei Turtoi, Jacques Colinge
Summary: This study confirms the heterogeneity of CRC-LM CAFs through single-cell transcriptomic analysis and proposes a model for recruiting different origins of CAFs to the liver in different liver malignancies. Additionally, the study finds that targeting LTBP2 with antibodies may help deplete ECM-remodeling CAFs in CRC-LMs.
Article
Immunology
Hassan Sadozai, Animesh Acharjee, Serenella Eppenberger-Castori, Beat Gloor, Thomas Gruber, Mirjam Schenk, Eva Karamitopoulou
Summary: The study reveals a T cell-inflamed tumor microenvironment in long-term survivors of PDAC, with distinct immune characteristics compared to non-long-term survivors. The TME of long-term survivors helps determine disease prognosis and offers potential for precision medicine.
FRONTIERS IN IMMUNOLOGY
(2021)
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)
Article
Oncology
Lenka N. C. Boyd, Katarina D. Andini, Godefridus J. Peters, Geert Kazemier, Elisa Giovannetti
Summary: Pancreatic ductal adenocarcinoma (PDAC) is an aggressive disease with a poor prognosis. The tumor microenvironment (TME) of PDAC, characterized by cancer-associated fibroblasts (CAFs), plays a dual role in tumor progression. Understanding the heterogeneity and plasticity of CAFs, as well as their behavior during PDAC progression, is crucial for improving therapeutic strategies for PDAC patients.
SEMINARS IN CANCER BIOLOGY
(2022)
Article
Immunology
Lan Yu, Yi Ding, Ting Wan, Ting Deng, He Huang, Jihong Liu
Summary: This study demonstrated the upregulation of CD47 in ovarian cancer and its correlation with poor overall survival and progression-free survival. CD47 expression levels were closely related to immune infiltration in ovarian cancer, particularly with Treg cells, monocytes, macrophages, and T cell exhaustion. The distinct cell components and distribution in primary and metastatic ovarian cancer may contribute to the tumor microenvironment heterogeneity.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Woosol Chris Hong, Da Eun Lee, Hyeon Woong Kang, Myeong Jin Kim, Minsoo Kim, Ju Hyun Kim, Sungsoon Fang, Hyo Jung Kim, Joon Seong Park
Summary: Pancreatic ductal adenocarcinoma (PDAC) is a deadly form of pancreatic cancer and the role of CD74 in PDAC is not well understood. Silencing CD74 in the pancreatic cancer cell line Capan-1 led to reduced cell proliferation, migration, invasion, increased apoptosis, and decreased expression and secretion of S100A8 and S100A9. The study suggests that CD74 may serve as a potential diagnostic biomarker and therapeutic target for pancreatic cancer.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Oncology
Mingwei Ma, Juan Sun, Zhen Liu, Siwen Ouyang, Zimu Zhang, Ziyang Zeng, Jie Li, Weiming Kang
Summary: This article reviews the recent research progress in prognostic prediction and the immune microenvironment of gastric cancer, and discusses the possibility of new therapeutic targets for gastric cancer.
FRONTIERS IN ONCOLOGY
(2022)
Article
Oncology
Miltiadis Tsesmelis, Kanishka Tiwary, Katja Steiger, Nadine Sperb, Melanie Gerstenlauer, Uta Manfras, Harald J. Maier, Patrick C. Hermann, Lap Kwan Chan, Thomas Wirth
Summary: The study investigated the role of NEMO/NF-kappa B signaling in the development and metastasis of pancreatic ductal adenocarcinoma (PDAC) using a genetically modified KPC mouse model. Deletion of NEMO in the mice prolonged survival, reduced liver metastasis, and highlighted NF-kappa B as a potential therapeutic target against PDAC.
Article
Neurosciences
Judith Stefanie Schlett, Melanie Mettang, Aladdin Skaf, Pavel Schweizer, Alina Errerd, Ephraim Alemayehu Mulugeta, Tabea Melissa Hein, Konstantinos Tsesmelis, Miltiadis Tsesmelis, Ulrike F. G. Buettner, Heinrich Wendt, Alireza Abaei, Volker Rasche, Vivien Prex, Ester Nespoli, Najwa Ouali Alami, Daniel Tews, Paul Walther, Deniz Yilmazer-Hanke, Franz Oswald, Leda Dimou, Thomas Wirth, Bernd Baumann
Summary: This study reveals the important role of chronic inflammation in regulating mature oligodendrocytes in the aging brain. Chronic NF-kappa B activation exacerbates neuroinflammation and leads to motor and cognitive impairments. Additionally, chronic NF-kappa B signaling promotes white matter degeneration and impairs myelin maintenance. Transcriptome analysis identifies activated stress responses and cellular senescence as key factors in chronic NF-kappa B activation. This study provides important insights into understanding age-dependent white matter degeneration and myelin defects in traumatic brain injury.
MOLECULAR NEURODEGENERATION
(2023)
Article
Cell Biology
Konstantinos Tsesmelis, Gandhari Maity-Kumar, Dana Croner, Jasmin Sprissler, Miltiadis Tsesmelis, Tabea Hein, Bernd Baumann, Thomas Wirth
Summary: Aging of the central nervous system (CNS) leads to motoric and cognitive decline and increases the probability for neurodegenerative disease development. Astrocytes fulfill central homeostatic functions in the CNS including regulation of immune responses and metabolic support of neurons and oligodendrocytes. Our study identifies maintenance of ROS homeostasis in astrocytes as a critical prerequisite for physiological CNS aging.
