Article
Multidisciplinary Sciences
Seon-Hee Kim, Eunjung Cho, Yu Kim, Chungyong Han, Beom K. Choi, Byoung S. Kwon
Summary: The study demonstrates that post-conditioning treatment with anti-CD4 can enhance the anti-tumor efficacy of adoptive T cell therapy (ACT) by promoting the expansion of IL-18R alpha(hi) CD8(+) T cells. This combination treatment accelerates proliferation and differentiation of tumor-reactive CD8(+) T cells and improves tumor suppression and host survival. The enrichment of polyfunctional IL-18R alpha(hi) CD8(+) T cells plays a key role in the induced tumor suppression, mediated by IL-18 signaling and TCR-MHC I interaction.
NATURE COMMUNICATIONS
(2021)
Article
Oncology
Luca Biasco, Natalia Izotova, Christine Rivat, Sara Ghorashian, Rachel Richardson, Aleks Guvenel, Rachael Hough, Robert Wynn, Bilyana Popova, Andre Lopes, Martin Pule, Adrian J. Thrasher, Persis J. Amrolia
Summary: Amrolia et al. characterized the clonal origins of long-term persistent CAR T cells from the CARPALL trial, demonstrating that central and effector memory cells in patients with long-term persistence remained highly polyclonal, while diversity dropped rapidly in patients with limited persistence. Shared integrants between the CAR T cell product and post-infusion revealed that T memory stem cell clones contributed substantially to the circulating CAR T cell pools during both early expansion and long-term persistence.
Review
Chemistry, Multidisciplinary
Yifan Xie, Feng Xie, Lei Zhang, Xiaoxue Zhou, Jun Huang, Fangwei Wang, Jin Jin, Long Zhang, Linghui Zeng, Fangfang Zhou
Summary: In the tumor microenvironment, immune cells such as T cells and B cells play crucial roles in anti-tumor immunotherapy. Understanding the functions of these cells can lead to novel therapies that induce specific anti-tumor immune responses, benefiting certain groups of patients. Various anti-tumor therapy approaches based on different immune cells are being explored for future applications in cancer treatment.
Review
Immunology
Yang Li, Gen Li, Jian Zhang, Xiaoli Wu, Xi Chen
Summary: Gamma delta T cells, a unique subgroup of T cells, can promote anti-tumor immune response but also potentially contribute to tumor progression. Studies have summarized and discussed their functions and effects in cancer, as well as reviewed recent anti-tumor immunotherapy based on gamma delta T cells, and identified existing problems and future prospects of this immunotherapy.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Dandan Yang, Zhihui Duan, Ping Yuan, Chengming Ding, Xiaoming Dai, Guodong Chen, Daichao Wu
Summary: TCR-engineered T cells have made significant progress in solid tumor therapy, with potential for further improvement in antigen selection and therapy strategies.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2023)
Article
Biochemistry & Molecular Biology
Keunok Jung, You-kyoung Jeon, Dae Hoon Jeong, Jung Mi Byun, Bjarne Bogen, Inhak Choi
Summary: The study identified VSIG4-expressing tumor-associated macrophages (TAMs) as negative regulators of anti-tumor immunity in the tumor microenvironment. These TAMs suppress T cell proliferation, cytokine production, and the cytotoxicity of CD8 thorn T cells.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2022)
Article
Chemistry, Multidisciplinary
Mohammad R. Nikmaneshi, James W. Baish, Hengbo Zhou, Timothy P. Padera, Lance L. Munn
Summary: This study uses mathematical modeling to explore the role of immune activation in anti-cancer immunity and its impact on response rates to immune checkpoint therapy. The results emphasize the importance of optimizing antigen production and T cell trafficking in lymph nodes for improved cancer immunotherapy.
Article
Oncology
Hongyan Wu, Xinyi Tang, Hyo Jin Kim, Shahrzad Jalali, Joshua C. Pritchett, Jose C. Villasboas, Anne J. Novak, Zhi-Zhang Yang, Stephen M. Ansell
Summary: The study found that intratumoral CD8(+) cells in FL are skewed toward effector cell subsets, exhibiting increased capacity to produce cytokines/granules compared to memory cell subsets, but with inferior proliferative and viability capacities. The distribution of different CD8(+) cell subsets is associated with the prognosis of patients with FL.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2021)
Article
Immunology
Nina Dumauthioz, Benjamin Tschumi, Mathias Wenes, Bastien Marti, Haiping Wang, Fabien Franco, Wenhui Li, Isabel C. Lopez-Mejia, Lluis Fajas, Ping-Chih Ho, Alena Donda, Pedro Romero, Lianjun Zhang
Summary: The overexpression of PGC-1 alpha favors central memory formation of CD8 T cells and enhances antitumor immunity. CD8 T cells with enhanced PGC-1 alpha expression show stronger antitumor immunity in a melanoma model.
CELLULAR & MOLECULAR IMMUNOLOGY
(2021)
Review
Immunology
Zhengguo Wu, Shang Li, Xiao Zhu
Summary: Cancer immunotherapy is a promising treatment to control and eliminate tumors, but it is currently only effective for certain types of tumors and faces challenges. By studying tumor microenvironment immunotherapy, the anti-tumor immunity can be enhanced, improving the effectiveness of immunotherapy.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Geriatrics & Gerontology
Waly Dioh, Vihang Narkar, Anurag Singh, Fady Malik, Luigi Ferrucci, Cendrine Tourette, Jean Mariani, Rob van Maanen, Roger A. Fielding
Summary: In recent years, new classes of therapies have been investigated, aiming to restore or improve physical functioning in older adults. These include Mas receptor agonists, regulators of mitophagy, skeletal muscle troponin activators, anti-inflammatory compounds, and targets of orphan nuclear receptors. This article summarizes recent developments on the function-promoting effects of these compounds, providing preclinical and clinical data on their safety and efficacy. The development of novel compounds in this area is expanding and may lead to a new treatment paradigm for age-associated mobility loss and disability.
JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES
(2023)
Article
Immunology
Peter M. Sullivan, Steven James Reed, Vandana Kalia, Surojit Sarkar
Summary: The study compared the phenotypic and functional characteristics of tumor-specific T cells and tumor-nonspecific bystander memory T cells within the solid tumor microenvironment, revealing that the latter can retain memory markers and functional cytokine production capabilities without antigenic stimulation. The findings suggest that T cells can persist and maintain functionality in different solid tumor environments, supporting the development of more effective TCR- and CAR-T cells through regulation of antigen and chemokine receptors.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Chemistry, Multidisciplinary
Handong Ma, Wanqi Fang, Qiaoming Li, Yuetong Wang, Steven X. Hou
Summary: This study reveals the molecular mechanisms of interactions between tumor cells and immune cells. The authors found that Arf1-ablated tumor cells release multiple factors, activating the triple pathways in DCs and promoting the production of various cytokines, thereby simultaneously promoting DC activation, T cell infiltration, cross-priming, and stemness.
Article
Oncology
Jiao Peng, Haifeng Huang, Qiuchan Huan, Chenghui Liao, Zebin Guo, Die Hu, Xiangchun Shen, Haitao Xiao
Summary: The deficiency of adiponectin (APN) maintains the activation of CD8(+) T cells to inhibit rhabdomyosarcoma growth by suppressing STAT3 activation.
FRONTIERS IN ONCOLOGY
(2022)
Article
Medicine, Research & Experimental
Hao Li, Yanling Guan, Chenchen Han, Yu Zhang, Yizhao Chen, Liping Jiang, Pingping Zhang, Xiu Chen, Wei Wei, Yang Ma
Summary: This article investigates the method of enhancing anti-tumor immunity by inhibiting TGF-beta receptor II in T cells. The results show that this method can reduce tumor load, promote T cell proliferation and differentiation, enhance cytotoxicity and anti-tumor effects, and reduce the proportion of regulatory T cells.
BIOMEDICINE & PHARMACOTHERAPY
(2022)
Article
Oncology
M. Strecker, K. Wlotzka, F. Strassheimer, B. Roller, G. Ludmirski, S. Konig, J. Roder, C. Opitz, T. Alekseeva, J. Reul, L. Sevenich, T. Tonn, W. S. Wels, J. P. Steinbach, C. J. Buchholz, M. C. Burger
Summary: This study explores a novel strategy for treating glioblastoma by targeting delivery of anti-PD-1 immunoadhesin (aPD-1) and HER2-specific NK cells, aiming to enhance treatment efficacy and reduce side effects.
Review
Oncology
Kilian B. Kennel, Muege Bozlar, Adalbert F. De Valk, Florian R. Greten
Summary: Tumor-associated inflammation (TAI) is a common feature in cancers, and cancer-associated fibroblasts (CAF) play a crucial role in modulating TAI. CAFs exhibit remarkable plasticity and can shift their phenotypes and functions in response to environmental changes. This review explores how CAFs contribute to tumor-promoting inflammation and suppress adaptive immunity, as well as the potential therapeutic strategies targeting CAFs in combination with immunotherapy.
CLINICAL CANCER RESEARCH
(2023)
Article
Gastroenterology & Hepatology
Claire Conche, Fabian Finkelmeier, Marina Pesic, Adele M. Nicolas, Tim W. Boettger, Kilian B. Kennel, Dominic Denk, Fatih Ceteci, Kathleen Mohs, Esther Engel, Oezge Canli, Yasamin Dabiri, Kai-Henrik Peiffer, Stefan Zeuzem, Gabriela Salinas, Thomas Longerich, Huan Yang, Florian R. Greten
Summary: Investigating the effect of ferroptosis in the tumour microenvironment, specifically focusing on liver cancer, to identify potential combinatory therapies. The study genetically altered GPx4 in mouse models for hepatocellular carcinoma and colorectal cancer to analyze the impact of ferroptosis on tumor cells and the immune response. The findings revealed a context-specific ferroptosis-induced immune response that could be used in the treatment of liver tumors and liver metastases.
Article
Multidisciplinary Sciences
Mark Schmitt, Fatih Ceteci, Jalaj Gupta, Marina Pesic, Tim W. Bottger, Adele M. Nicolas, Kilian B. Kennel, Esther Engel, Matthias Schewe, Asude Callak Kirisozu, Valentina Petrocelli, Yasamin Dabiri, Julia Varga, Mallika Ramakrishnan, Madina Karimova, Andrea Ablasser, Toshiro Sato, Melek C. Arkan, Frederic J. de Sauvage, Florian R. Greten
Summary: In solid tumors, dying cancer cells release ATP and activate paracrine effects on neighboring tumor epithelial cells, triggering an mTOR-dependent pro-survival program and rendering the surviving epithelial cells sensitive to mTOR inhibition. This dependency is due to increased production of reactive oxygen species and DNA damage associated with neighboring cell death.
Article
Neurosciences
Danny Baltissen, Charlotte S. Bold, Lena Rehra, Marija Banicevic, Justus Fricke, Jennifer Just, Susann Ludewig, Christian J. Buchholz, Martin Korte, Ulrike C. Mueller
Summary: The Tau protein is phosphorylated by multiple kinases and the accumulation of hyperphosphorylated Tau species is a major characteristic of Alzheimer's disease (AD). AD is also characterized by the presence of A beta plaques derived from the beta-amyloid precursor protein APP. APP processing along the non-amyloidogenic pathway results in the secretion of neurotrophic APPs alpha, which has therapeutic effects in transgenic AD model mice. In this study, the researchers investigated the potential of APPs alpha to regulate the Tau kinases GSK3 beta and CDK5 in a mouse model of tauopathy, and found that APPs alpha restored normal kinase activity and mitigated Tau-induced pathology.
FRONTIERS IN CELLULAR NEUROSCIENCE
(2023)
Article
Pathology
Stefanie Jaitner, Elise Pretzsch, Jens Neumann, Achim Schaeffauer, Matthias Schiemann, Martin Angele, Joerg Kumbrink, Sarah Schwitalla, Florian R. Greten, Lydia Brandl, Frederick Klauschen, David Horst, Thomas Kirchner, Andreas Jung
Summary: Tumor stem cells are important in colorectal cancer (CRC) as they contribute to the development of tumors and their spread. Olfactomedin 4 (OLFM4) has been suggested as a biomarker for cancer stemness and prognosis in gastrointestinal tumors. However, this study found that OLFM4 expression in human CRC is characteristic of differentiation marker expression but does not drive carcinogenesis or metastatic spread. These findings suggest that OLFM4 may not be a suitable target for therapeutic intervention in CRC.
JOURNAL OF PATHOLOGY CLINICAL RESEARCH
(2023)
Review
Cell Biology
Robert Schierwagen, Wenyi Gu, Angela Brieger, Bernhard Bruene, Sandra Ciesek, Ivan Dikic, Stefanie Dimmeler, Gerd R. Geisslinger, Florian Greten, Eva Hermann, Eberhard Hildt, Volkhard A. J. Kempf, Sabine Klein, Ina Koch, Heiko Muehl, Volker Mueller, Kai-Henrik Peiffer, Roxane-Isabelle Kestner, Albrecht Piiper, Gernot Rohde, Klaus H. Scholich, Marcel Schulz, Holger Storf, Tuna Toptan, Mariuca Vasa-Nicotera, Maria J. G. T. Vehreschild, Andreas J. Weigert, Peter Wild, Stefan Zeuzem, Cornelius Engelmann, Liliana Schaefer, Christoph Welsch, Jonel Trebicka
Summary: Liver cirrhosis is a final stage of chronic liver diseases with a 2% global mortality rate. In Europe, the age-standardized mortality from liver cirrhosis ranges from 10 to 20%, which is attributed to both liver cancer development and acute deterioration in the patient's overall condition. The development of complications such as ascites, variceal bleeding, bacterial infections, or hepatic encephalopathy leads to acute decompensation and often progresses to acute-on-chronic liver failure (ACLF) through different precipitating events. However, the pathogenesis of ACLF remains poorly understood, and there are no specific therapy options apart from general intensive care interventions.
AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY
(2023)
Article
Medicine, Research & Experimental
Angela H. Braun, Annika M. Frank, Naphang Ho, Christian J. Buchholz
Summary: CD3-targeted lentiviral vectors (CD3-LVs) effectively transduce human T lymphocytes and activate them. The use of Src/Abl tyrosine kinase inhibitor dasatinib enhances gene delivery by T cell-targeted LVs. Dasatinib treatment prior to incubation with CD3-LV improves reporter gene delivery and transduction into non-activated target cells.
MOLECULAR THERAPY-METHODS & CLINICAL DEVELOPMENT
(2023)
Article
Multidisciplinary Sciences
Larsen Vornholz, Sophie E. Isay, Zsuzsanna Kurgyis, Daniel C. Strobl, Patricia Loll, Mohammed H. Mosa, Malte D. Luecken, Michael Sterr, Heiko Lickert, Christof Winter, Florian R. Greten, Henner F. Farin, Fabian J. Theis, Juergen Ruland
Summary: Immune checkpoint inhibitors (ICIs) enhance anticancer immunity by releasing repressive signals into tumor microenvironments (TMEs). This study found that the superior antitumor immune response of mismatch repair (MMR)-deficient colorectal cancer (CRC) required tumor cell-intrinsic activation of cGAS-STING signaling triggered by genomic instability. In MMR-proficient CRC, genetically encoded gain-of-function STING was sufficient to induce cancer cell-intrinsic interferon signaling, local activation of antigen-presenting cells, recruitment of effector lymphocytes, and sensitization of previously cold TMEs to ICI therapy in vivo.
Article
Gastroenterology & Hepatology
Boonsanay Boonsanay, Mohammed H. Mosa, Mario Looso, Dieter Weichenhan, Fatih Ceteci, Lorenz Pudelko, Andre Lechel, Christian S. Michel, Carsten Kuenne, Henner F. Farin, Christoph Plass, Florian R. Greten
Summary: SUV420H2 is an important regulator of epithelial cell plasticity and its loss contributes to right-sided colorectal tumorigenesis through epigenetic regulation of chromatin compaction. Reduced levels of H4K20me3 and increased chromatin accessibility are observed in patient-derived right-sided colorectal cancer organoids. Inhibition of histone demethylases can lead to re-compaction of chromatin and selective growth inhibition in right-sided colorectal tumors.