Article
Oncology
Amanda M. Clark, Haley L. Heusey, Linda G. Griffith, Douglas. A. Lauffenburger, Alan Wells
Summary: Metastatic breast cancer with liver involvement is a largely incurable and fatal disease, with a subset of disseminated tumor cells potentially lying dormant for years before re-emerging. IP-10, a CXCR3 ligand, has been found to be elevated in metastatic TNBC breast cancer cells, triggering their emergence within the liver metastatic niche. This pathway could be a target for maintaining dormancy in breast cancer treatment.
FRONTIERS IN ONCOLOGY
(2021)
Article
Oncology
Shivan Sivakumar, Enas Abu-Shah, David J. Ahern, Edward H. Arbe-Barnes, Ashwin K. Jainarayanan, Nagina Mangal, Srikanth Reddy, Aniko Rendek, Alistair Easton, Elke Kurz, Michael Silva, Zahir Soonawalla, Lara R. Heij, Rachael Bashford-Rogers, Mark R. Middleton, Michael L. Dustin
Summary: The study found that T cells play a crucial role in pancreatic cancer, with regulatory T cells expressing high levels of immune inhibitory proteins, and CD8(+) T cells showing low PD-1 expression in an exhausted state. These findings provide a basis for the rational design of a new generation of therapeutic strategies for pancreatic cancer.
Article
Oncology
Carmen Mota Reyes, Elke Demir, Kaan Cifcibasi, Rouzanna Istvanffy, Helmut Friess, Ihsan Ekin Demir
Summary: Regulatory T cells (Treg) are a major immunosuppressive cell subset in the pancreatic tumor microenvironment, influencing tumor growth by acting either directly on cancer cells or inhibiting effector immune cells. Tregs form a partially redundant network with other immunosuppressive cells like myeloid-derived suppressor cells (MDSC), enhancing tumor immunosuppression and resistance to immunotherapy. Preclinical studies show Treg depletion leads to simultaneous decrease in MDSCs in early tumors, but an inverse association in advanced PCa, prompting comprehensive analysis of PCa's immunosuppressive profile throughout tumorigenesis.
Review
Cell Biology
Zhilin Zhang, Huan Zhang, Tian Liu, Tian Chen, Daorong Wang, Dong Tang
Summary: Pancreatic cancer is associated with strong therapeutic resistance and poor prognosis, with activated pancreatic stellate cells (PSC) playing a crucial role in the malignant progression. By analyzing PSC population heterogeneity, researchers have identified two subtypes - myofibroblastic and inflammatory PSC - that cooperate to create a microenvironment suitable for cancer cell survival, potentially offering more effective treatment options for pancreatic cancer patients.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Engineering, Biomedical
Rongze Wang, Keze Hong, Qiaoyun Zhang, Jianrong Cao, Tao Huang, Zecong Xiao, Yong Wang, Xintao Shuai
Summary: Pancreatic ductal adenocarcinoma (PDAC) is a type of cancer with poor response to immunotherapy due to the dense extracellular matrix and activation of pancreatic stellate cells (PSCs). In this study, a nanodrug was developed to simultaneously inactivate PSCs and suppress CXCL12, leading to remodeling of the tumor microenvironment, increased infiltration of cytotoxic T cells, and improved immunotherapy outcome.
ACTA BIOMATERIALIA
(2023)
Review
Cell Biology
Ke-jia Wu, Qu-fei Qian, Jin-ren Zhou, Dong-lin Sun, Yun-fei Duan, Xi Zhu, Kurt Sartorius, Yun-jie Lu
Summary: The human liver plays crucial roles in synthesizing extracellular matrix (ECM) and regulating fibrogenesis for maintaining homeostasis. Chronic liver injury induces fibrogenesis due to the imbalance between ECM accumulation and fibrosis resolution. Liver diseases that cause fibrogenesis are associated with various risk factors, including hepatitis infection, schistosomiasis, alcohol, certain drugs, toxicants, diabetes, and obesity. Hepatic stellate cells (HSCs) activation, which generate and accumulate ECM, is a key event in liver fibrosis. The paper reviews the dual role of regulatory T-cells (Tregs) in liver fibrogenesis, including their promotion of immunosuppression and activation of fibrosis. Understanding the contradictory roles of Tregs in different immune microenvironments and molecular pathways is important for managing liver fibrosis.
CELL DEATH DISCOVERY
(2023)
Review
Oncology
Zhengfeng Wang, Ru He, Shi Dong, Wence Zhou
Summary: Pancreatic cancer is a highly malignant gastrointestinal carcinoma with late detection, high mortality rates, poor patient prognosis, and a lack of effective treatments. Pancreatic stellate cells, a significant component of the tumor microenvironment, play a crucial role in modulating this environment and promoting cancer progression. This paper reviews the mechanisms by which pancreatic stellate cells inhibit antitumor immune responses and discusses preclinical studies focusing on these cells, aiming to provide theoretical references for the development of new therapeutic approaches for pancreatic cancer.
FRONTIERS IN ONCOLOGY
(2023)
Article
Oncology
Thomas Brouwer, Marieke Ijsselsteijn, Jan Oosting, Dina Ruano, Manon van der Ploeg, Frederike Dijk, Bert Bonsing, Arantza Farina, Hans Morreau, Alexander Vahrmeijer, Noel de Miranda
Summary: The infiltration of regulatory T cells (Tregs) in pancreatic ductal adenocarcinomas (PDAC) is associated with better overall survival of patients, independent of cytotoxic T cell infiltration and the transcriptomic profiles of their respective tumors.
Article
Gastroenterology & Hepatology
Yu Tanaka, Shin Hamada, Ryotaro Matsumoto, Keiko Taguchi, Masayuki Yamamoto, Atsushi Masamune
Summary: Systemic Nrf2 deletion decreases pancreatic cancer progression in a mutant K-ras/p53-expressing mouse model, with pancreatic stellate cells (PSCs) playing a role in this process. Nrf2-deleted PSCs exhibit lower proliferative and migration capacity, and show reduced growth-stimulating effects on pancreatic cancer cells.
AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY
(2021)
Article
Oncology
Lei Zhu, Jianmei Yin, Fuhong Zheng, Lianfeng Ji, Yingqing Yu, Haibo Liu
Summary: Activated pancreatic stellate cells (PSCs) with increased proliferation and migration ability are the partners in crime with pancreatic cancer cells. ASIC1 overexpression induced by pancreatic cancer cells enhances the proliferative and migratory abilities of PSCs, which can be weakened by ASIC1 inhibition. Additionally, ASIC1 participates in the regulation of PSCs proliferation and migration induced by cancer cells via the ERK pathway.
Article
Immunology
Patricia Ramos-Ramirez, Carina Malmhall, Omar Tliba, Madeleine Radinger, Apostolos Bossios
Summary: Adiponectin/AdipoR1 axis promotes IL-10 release by Tregs, mainly in Helios(-) Tregs, and the effect was amplified by T2 inflammation in Helios(+) Tregs. This suggests a potential role of adiponectin in regulating Treg function in human inflammatory conditions.
FRONTIERS IN IMMUNOLOGY
(2021)
Review
Immunology
Michael L. Dixon, Jonathan D. Leavenworth, Jianmei W. Leavenworth
Summary: Regulatory T-cells, particularly effector Tregs (eTregs), play a crucial role in maintaining self-tolerance and tissue homeostasis, with potential implications in tumor development. Understanding the mechanisms that modulate the stability and suppressive function of tumoral Tregs, such as eTregs and T-FR cells, can lead to the development of more effective cancer immunotherapies that target the tumor microenvironment while minimizing systemic side effects.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Immunology
Fatemeh Nezhad Shamohammadi, Mahboubeh Yazdanifar, Mona Oraei, Mohammad H. Kazemi, Azam Roohi, Seyedeh Mahya Shariat Razavi, Farhad Rezaei, Farzad Parvizpour, Yalda Karamlou, Haideh Namdari
Summary: γδT cells are rare lymphocytes that play a cogent role in immune responses. They have anti-tumor activity, but there is controversy regarding their effects in pancreatic cancer. Depending on the local microenvironment, γδT cells can differentiate into cells that promote or suppress tumors. In immunologically cold tumors like pancreatic cancer, γδT cells are more likely to exhibit an immunosuppressive phenotype.
INTERNATIONAL IMMUNOPHARMACOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Di Wu, Weibo Chen, Yang Yang, Yi Qin, Guangchen Zu, Yue Zhang, Yong An, Donglin Sun, Xiaowu Xu, Xuemin Chen
Summary: This study investigates the role of PITX2 in pancreatic stellate cells (PSCs) in the progression of pancreatic cancer and reveals that silencing PITX2 in PSCs inhibits the growth, migration, and invasion of pancreatic cancer cells. Additionally, high expression of PITX2 in stromal cells is correlated with poor prognosis in patients with pancreatic cancer.
ACTA BIOCHIMICA ET BIOPHYSICA SINICA
(2023)
Review
Oncology
Christopher Tay, Atsushi Tanaka, Shimon Sakaguchi
Summary: Regulatory T cells (Tregs) in tumor tissues can be selectively targeted to enhance anti-tumor immune responses, while maintaining immune homeostasis in healthy organs. Current strategies such as immune checkpoint blockade (ICB) antibodies and differential targeting of surface and intracellular molecules show promise in this regard. Combining Treg targeting with ICB antibodies may enhance the efficacy of cancer immunotherapy.
Article
Computer Science, Interdisciplinary Applications
Russell Bates, Benjamin Irving, Bostjan Markelc, Jakob Kaeppler, Graham Brown, Ruth J. Muschel, Sir Michael Brady, Vicente Grau, Julia A. Schnabel
IEEE TRANSACTIONS ON MEDICAL IMAGING
(2019)
Article
Oncology
Hannah Yejin Kim, Janna K. Duong, Maria Gonzalez, Georgina V. Long, Alexander M. Menzies, Helen Rizos, Su Yin Lim, Jenny Lee, Alan V. Boddy
CANCER CHEMOTHERAPY AND PHARMACOLOGY
(2019)
Article
Oncology
Su Y. Lim, Jenny H. Lee, Tuba N. Gide, Alexander M. Menzies, Alexander Guminski, Matteo S. Carlino, Edmond J. Breen, Jean Y. H. Yang, Shila Ghazanfar, Richard F. Kefford, Richard A. Scolyer, Georgina V. Long, Helen Rizos
CLINICAL CANCER RESEARCH
(2019)
Article
Oncology
Tuba N. Gide, Camelia Quek, Alexander M. Menzies, Annie T. Tasker, Ping Shang, Jeff Holst, Jason Madore, Su Yin Lim, Rebecca Velickovic, Matthew Wongchenko, Yibing Yan, Serigne Lo, Matteo S. Carlino, Alexander Guminski, Robyn P. M. Saw, Angel Pang, Helen M. McGuire, Umaimainthan Palendira, John F. Thompson, Helen Rizos, Ines Pires da Silva, Marcel Batten, Richard A. Scolyer, Georgina V. Long, James S. Wilmott
Article
Oncology
Alex Gordon-Weeks, Su Yin Lim, Arseniy Yuzhalin, Serena Lucotti, Jenny Adriana Francisca Vermeer, Keaton Jones, Jianzhou Chen, Ruth J. Muschel
Article
Oncology
Zizhen Ming, Su Yin Lim, Richard F. Kefford, Helen Rizos
PIGMENT CELL & MELANOMA RESEARCH
(2020)
Correction
Multidisciplinary Sciences
Jin-Woong Lee, Woon Bae Park, Jin Hee Lee, Satendra Pal Singh, Kee-Sun Sohn
NATURE COMMUNICATIONS
(2020)
Article
Cell Biology
Jenny A. F. Vermeer, Jonathan Ient, Bostjan Markelc, Jakob Kaeppler, Lydie M. O. Barbeau, Arjan J. Groot, Ruth J. Muschel, Marc A. Vooijs
DISEASE MODELS & MECHANISMS
(2020)
Article
Oncology
Aaron T. Ciner, Keaton Jones, Ruth J. Muschel, Pnina Brodt
Summary: Liver metastases play a significant role in cancer-related mortality, with the liver's unique microenvironment posing a dual role in promoting cancer cell survival. Understanding the role of the liver microenvironment has led to the development of innovative strategies for targeting liver metastatic disease.
SEMINARS IN CANCER BIOLOGY
(2021)
Article
Multidisciplinary Sciences
Jae Hong Im, Jon N. Buzzelli, Keaton Jones, Fanny Franchini, Alex Gordon-Weeks, Bostjan Markelc, Jianzhou Chen, Jin Kim, Yunhong Cao, Ruth J. Muschel
NATURE COMMUNICATIONS
(2020)
Review
Biochemistry & Molecular Biology
Zizhen Ming, Su Yin Lim, Helen Rizos
Article
Biochemistry & Molecular Biology
Su Yin Lim, Sara Alavi, Zizhen Ming, Elena Shklovskaya, Carina Fung, Ashleigh Stewart, Helen Rizos
Summary: Our study found that tumor necrosis factor alpha (TNF alpha) can influence the differentiation status and immune inhibition of melanoma cells, with different impacts on different melanoma cells. TNF alpha showed poor induction of antigen presentation molecules but readily induced the PD-L2 immune checkpoint in melanoma cells. Our results suggest that TNF alpha promotes dynamic changes in melanoma cells that may favor immunotherapy resistance.
Letter
Oncology
Su Yin Lim, Bernadette Pedersen, Helen Rizos
PIGMENT CELL & MELANOMA RESEARCH
(2022)
Article
Dermatology
Zizhen Ming, Su Yin Lim, Ashleigh Stewart, Bernadette Pedersen, Elena Shklovskaya, Alexander M. Menzies, Matteo S. Carlino, Richard F. Kefford, Jenny H. Lee, Richard A. Scolyer, Georgina V. Long, Helen Rizos
Summary: Immunotherapy targeting PD-1 and/or CTLA4 can lead to durable responses in some melanoma patients. However, treatment resistance and lack of response are common. This study identifies a vulnerability in melanoma driven by immune cell activity, providing potential strategies for combination therapies.
JOURNAL OF INVESTIGATIVE DERMATOLOGY
(2023)
Article
Oncology
Elena Shklovskaya, Jenny H. Lee, Su Yim Lim, Ashleigh Stewart, Bernadette Pedersen, Peter Ferguson, Robyn P. M. Saw, John F. Thompson, Brindha Shivalingam, Matteo S. Carlino, Richard A. Scolyer, Alexander M. Menzies, Georgina Long, Richard F. Kefford, Helen Rizos
