Review
Immunology
Xiaoting Zhou, Yanghong Ni, Xiao Liang, Yi Lin, Biao An, Xiang He, Xia Zhao
Summary: Immune checkpoint blockade has revolutionized cancer treatment, but drug resistance limits its effectiveness. This study investigates the mechanisms of resistance and proposes strategies to enhance the efficacy of immune checkpoint blockade.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Immunology
Zihan Zhao, Siyang Liu, Rui Sun, Wenjie Zhu, Yulin Zhang, Tianyao Liu, Tianhang Li, Ning Jiang, Hongqian Guo, Rong Yang
Summary: Bladder cancer is a highly malignant tumor with limited improvement in prognosis and survival rates. Immune checkpoint inhibitors have revolutionized the treatment of bladder cancer, but their clinical application is limited by low response rates. This study investigated the combination of oxaliplatin and anti-PD-1 inhibitor in bladder cancer mouse models and found that this combination therapy was more efficient than medication alone.
FRONTIERS IN IMMUNOLOGY
(2023)
Review
Materials Science, Multidisciplinary
Xin Li, Yu Zhen, Shanshan Li
Summary: This article reviews the significance of immune checkpoint blockade, photodynamic therapy, and nanotechnology in cancer treatment, highlighting the promising results of their combination in preclinical models and potential clinical applications.
MATERIALS & DESIGN
(2021)
Article
Gastroenterology & Hepatology
Zhengqing Lei, Weihu Ma, Anfeng Si, Yuhua Zhang, Facai Yang, Qiushi Yu, Haolan Tang, Qianru Xiao, Jiahua Zhou, Kui Wang, Yufu Tang, Tao Han, Guowen Yin, Jinhong Chen, Xiufeng Liu, Hua Zhao, Decai Yu, Tao Luo, Qing Wang, Maolin Yan, Xianhai Mao, Jing Li, Kai Wang, Jingdong Li, Yongyi Zeng, Dequan Ding, Tingsong Chen, Xiaofeng Wu, Yongxiang Xia, Kang Wang, Weixing Guo, Guangyu Zhu, Shan Gao, Norbert Hueser, Wan Y. Lau, Tianqiang Song, Shuqun Cheng, Feng Shen, Zhangjun Cheng
Summary: This study compared the efficacy of different anti-PD-1 combination therapies as the first-line treatment for uICC. The results showed that ICI-chemo and ICI-target therapies had better survival outcomes and fewer adverse events compared to chemotherapy. ICI-target-chemo had similar efficacy to ICI-chemo but resulted in more adverse events.
ALIMENTARY PHARMACOLOGY & THERAPEUTICS
(2023)
Review
Immunology
Zaoqu Liu, Yuqing Ren, Siyuan Weng, Hui Xu, Lifeng Li, Xinwei Han
Summary: Immunotherapy is a promising treatment for cancer, but most patients do not respond or develop resistance. In order to improve therapeutic effects, combination therapy has emerged, with the combination of immune checkpoint inhibition and epigenetic therapy being one such strategy.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Biotechnology & Applied Microbiology
Jing Zhan, Manli Zhang, Lili Zhou, Chuan He
Summary: The present study developed a synergistic strategy by combining in situ tumor vaccines, gene-mediated downregulation of tumor angiogenesis, and anti-PD-L1 therapy to address several key problems in tumor immunotherapy. This strategy can enhance the activation of effector T cells, improve tumor invasion and immune killing ability, and increase treatment response rate.
FRONTIERS IN BIOENGINEERING AND BIOTECHNOLOGY
(2023)
Article
Immunology
Qi-jie Zhang, Jiao-chen Luan, Le-bin Song, Rong Cong, Cheng-jian Ji, Xiang Zhou, Jia-dong Xia, Ning-hong Song
Summary: The study found no difference in efficacy between elderly and young patients in most cancer types, except for melanoma patients receiving anti-PD-1 therapy. Elderly patients showed higher treatment response rate and more favorable prognosis in certain cancer types, potentially attributed to their high mutational properties. This suggests that modulating immune function could be beneficial to immunotherapy in elderly patients.
FRONTIERS IN IMMUNOLOGY
(2021)
Review
Oncology
I-Tsu Chyuan, Ching-Liang Chu, Ping-Ning Hsu
Summary: Immune checkpoint inhibitors (ICIs) have revolutionized cancer therapy by expanding knowledge of anticancer immunity and introducing breakthroughs in cancer treatment. Exploration of cellular and molecular factors within the tumor microenvironment (TME) to understand immunotherapy resistance mechanisms has led to the development of novel combination strategies for cancer immunotherapy.
Review
Immunology
Yujie Zhao, Xu Liu, Xinyu Liu, Jing Yu, Xin Bai, Xi Wu, Xinyu Guo, Zhihui Liu, Xiaowei Liu
Summary: This review summarizes the mechanism of phototherapy in cancer immunotherapy and discusses the recent advances in the development of phototherapy combined with ICB therapy to treat malignant tumors. The authors also outline the significant progress of phototherapy combined with targeted therapy or chemotherapy to improve ICB, and analyze the current challenges of this novel combination treatment regimen. The authors believe that the next-generation technology breakthrough in cancer treatment may come from this combinational win-win strategy of photoimmunotherapy.
FRONTIERS IN IMMUNOLOGY
(2022)
Review
Immunology
Sijia Ren, Xinxin Xiong, Hua You, Jianfei Shen, Penghui Zhou
Summary: Combining immunotherapy with anti-angiogenesis can transform the tumor microenvironment from immunosuppressive to immune-supportive, increasing the infiltration and activation of immune cells. Therefore, this combination is a promising strategy for cancer treatment.
FRONTIERS IN IMMUNOLOGY
(2021)
Review
Biochemistry & Molecular Biology
Katerina Kalkusova, Sindija Smite, Elea Darras, Pavla Taborska, Dmitry Stakheev, Luca Vannucci, Jirina Bartunkova, Daniel Smrz
Summary: The immune checkpoint inhibitors are crucial in cancer immunotherapy, but their efficacy is limited in solid tumors. Mast cells and dendritic cells play important roles in the tumor immune microenvironment and controlling these cells may help overcome the resistance of solid tumors to immunotherapy.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Oncology
Frederick J. Kohlhapp, Dipica Haribhai, Rebecca Mathew, Ryan Duggan, Paul A. Ellis, Rui Wang, Elisabeth A. Lasater, Yan Shi, Nimita Dave, Jacob J. Riehm, Valerie A. Robinson, An D. Do, Yijin Li, Christine J. Orr, Deepak Sampath, Aparna Raval, Mark Merchant, Anahita Bhathena, Ahmed Hamed Salem, Keith M. Hamel, Joel D. Leverson, Cherrie Donawho, William N. Pappano, Tamar Uziel
Summary: Venetoclax, a selective BCL2 inhibitor, can enhance the anticancer efficacy of immune checkpoint inhibitors by increasing PD-1+ T effector memory cells in mouse models. It does not impair human T-cell function and can provide a survival advantage in effector T cells, indicating its potential in combination with ICIs for cancer therapy.
Article
Pharmacology & Pharmacy
Yingying Li, Kaiyuan Ni, Christina Chan, Nining Guo, Taokun Luo, Wenbo Han, August Culbert, Ralph R. Weichselbaum, Wenbin Lin
Summary: The combination of radiotherapy (RT) and immunotherapy, along with DMAMCL sensitization, significantly enhances anti-cancer efficacy by increasing tumor-infiltrating CD4 and CD8 T cells, and establishing immune memory.
ADVANCED THERAPEUTICS
(2022)
Article
Medicine, Research & Experimental
Dong Shao, Yaping Chen, Hao Huang, Yingting Liu, Junjun Chen, Dawei Zhu, Xiao Zheng, Lujun Chen, Jingting Jiang
Summary: This study demonstrates that the combination therapy of LAG3 blockade and microwave ablation (MWA) is a unique treatment strategy for certain solid tumors, which can alter the tumor microenvironment and extend survival.
JOURNAL OF TRANSLATIONAL MEDICINE
(2022)
Review
Surgery
Xavier L. Baldwin, Philip M. Spanheimer, Stephanie Downs-Canner
Summary: The immune system is a complex and interconnected system that protects the host from foreign pathogens. CD8+ T cells have the ability to directly kill tumor cells, but their killing capabilities can be inhibited by checkpoint molecules. The development of medications that block these checkpoint molecules has revolutionized the treatment of certain cancers, but immunotherapy-related toxicities are becoming more common and may impact surgical planning.
JOURNAL OF SURGICAL RESEARCH
(2023)
Review
Immunology
Mads Hald Andersen
Summary: Identifying and characterizing tumor antigens are crucial for developing anti-cancer immunotherapy. Traditional tumor-associated antigens (TAAs) are mainly expressed in tumor cells, while tumor-specific antigens (TSAs) are unique to tumor cells. Recent studies have focused on patient-specific neoantigens, which are highly immunogenic due to their absence in normal tissues. In addition, the discovery of anti-regulatory T cells (anti-Tregs) has led to the identification of tumor microenvironment antigens (TMAs) that can be targeted for immunotherapy. TMAs not only directly attack tumor cells but also modulate the tumor microenvironment, making it more immunocompetent and hostile to tumors. Unlike TAAs and TSAs, TMAs are also expressed in non-transformed cells, providing the opportunity to affect tumors with low levels of surface human leukocyte antigen (HLA) expression. This review discusses the characteristics, differences, and advantages of TMAs compared to traditional tumor antigens and highlights the potential of using TMAs in immune modulatory vaccines as a promising approach to immunotherapy.
SEMINARS IN IMMUNOPATHOLOGY
(2023)
Editorial Material
Infectious Diseases
Mads Hald Andersen
Article
Nanoscience & Nanotechnology
Carmen Radeke, Raphael Pons, Marko Mihajlovic, Jonas R. Knudsen, Sarkhan Butdayev, Paul J. Kempen, Charis-Patricia Segeritz, Thomas L. Andresen, Christian K. Pehmoller, Thomas E. Jensen, Johan U. Lind
Summary: In order to achieve the automated fabrication of complex tissue mimicking constructs through 3D bioprinting, it is necessary to develop bioinks that are not only printable and biocompatible but also have integrated cell-instructive properties. Here, we present a scalable technique for generating nanofiber 3D printing inks with unique tissue-guiding capabilities. By tailoring the size and dispersibility of cellulose fibrils, we are able to create nanofibers that match the size and dimensions of natural collagen fibers, allowing for the orientation of cells and the spatial organization of engineered tissues during printing.
ACS APPLIED MATERIALS & INTERFACES
(2023)
Article
Oncology
Arianna Draghi, Mario Presti, Agnete W. P. Jensen, Christopher A. Chamberlain, Benedetta Albieri, Anne-Christine K. Rasmussen, Mads H. Andersen, Michael D. Crowther, Inge Marie Svane, Marco Donia
Summary: Our study demonstrates that exploiting tumor-specific cytotoxic CD4(+) TILs could help overcome resistance to ICB mediated by IFN gamma-signaling loss in MHCIIconst(+) melanomas.
CLINICAL CANCER RESEARCH
(2023)
Article
Biochemistry & Molecular Biology
Mia Danielsen, Paul Joseph Kempen, Thomas Lars Andresen, Andrew James Urquhart
Summary: The development of new and improved formulations for biopharmaceuticals is driven by the growing interest in this class of therapeutics and the challenges in formulation and delivery. Nanoclusters (NCs) are a type of formulation strategy where the biopharmaceutical is clustered reversibly to function as both the therapeutic and the vehicle. In this study, insulin NCs (INCs) were formulated using a new methodology of first crosslinking proteins followed by desolvation. The crosslinked INCs showed controlled synthesis, good biocompatibility, and slightly lower potency compared to the unmodified protein.
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
(2023)
Article
Nanoscience & Nanotechnology
Marina Simon, Jesper Tranekjaer Jorgensen, Kamilla Norregaard, Jonas Rosager Henriksen, Gael Clergeaud, Thomas L. Andresen, Anders Elias Hansen, Andreas Kjaer
Summary: Traditional cancer treatments are often insufficient to achieve complete responses, so combination therapies are commonly used. Nanoparticle-based photothermal therapy (PTT) is a promising add-on treatment that uses localized hyperthermia to kill cancer cells. In this study, we evaluated the combination of gold nanoshell-based PTT and liposomal doxorubicin for colorectal cancer treatment.
INTERNATIONAL JOURNAL OF NANOMEDICINE
(2023)
Article
Chemistry, Multidisciplinary
Adam Coln Hundahl, Arjen Weller, Jannik Bruun Larsen, Claudia U. Hj, Morten B. Hansen, Ann-Kathrin Muendler, Astrid Knuhtsen, Kasper Kristensen, Eva C. Arnspang, Thomas Lars Andresen, Kim I. Mortensen, Rodolphe Marie
Summary: Oral drug delivery is the preferred administration route for most drugs, but it is limited for biologics due to the intestinal barrier. One strategy to improve the absorption is chemical modification through lipidation. However, the mechanistic understanding of the effect is largely unexplored. This study developed a method to quantify peptide transport through a monolayer of Caco-2 cells and investigated the effects of lipidation on transport mechanism.
JOURNAL OF CONTROLLED RELEASE
(2023)
Editorial Material
Immunology
Mads Hald Andersen
SEMINARS IN IMMUNOPATHOLOGY
(2023)
Article
Immunology
Sofie Kirial Mork, Per Kongsted, Marie Christine Wulff Westergaard, Benedetta Albieri, Joachim Stoltenborg Granhoj, Marco Donia, Evelina Martinenaite, Morten Orebo Holmstroem, Kasper Madsen, Anders H. Kverneland, Julie Westerlin Kjeldsen, Rikke Boedker Holmstroem, Cathrine Lund Lorentzen, Nis Norgaard, Lars Vibe Andreasen, Grith Kroyer Wood, Dennis Christensen, Michael Schantz Klausen, Sine Reker Hadrup, Per Thor Straten, Mads Hald Andersen, Inge Marie Svane
Summary: This study evaluated the tolerability and safety of a vaccine using Bcl-XL-peptide and CAF((R))09b as an adjuvant in patients with hormone-sensitive prostate cancer. The optimal route of administration and vaccine immunogenicity were also assessed. The vaccine was found to be feasible and safe, and it was able to induce immune responses. IP administration led to earlier and stronger vaccine-specific immune responses compared to IM administration.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Immunology
Jacob Handlos Grauslund, Morten Orebo Holmstrom, Evelina Martinenaite, Thomas Landkildehus Lisle, Hannah Jorinde Glockner, Daniel El Fassi, Uffe Klausen, Rasmus E. J. Mortensen, Nicolai Jorgensen, Lasse Kjaer, Vibe Skov, Inge Marie Svane, Hans Carl Hasselbalch, Mads Hald Andersen
Summary: The study tested the safety and efficacy of dual vaccination with ARG1- and PD-L1-derived peptides in JAK2 V617F-mutated MPN patients. The vaccines were found to be safe and induced strong T-cell responses in all patients, indicating their potential as a treatment option.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Immunology
Thomas Morgan Hulen, Christina Friese, Nikolaj Pagh Kristensen, Joachim Stoltenborg Granhoj, Troels Holz Borch, Marlies J. W. Peeters, Marco Donia, Mads Hald Andersen, Sine Reker Hadrup, Inge Marie Svane, Ozcan Met
Summary: Checkpoint inhibition (CPI) therapy and adoptive cell therapy with autologous tumor-infiltrating lymphocytes (TIL-based ACT) have shown to be highly effective immunotherapies for metastatic melanoma treatment. In this study, we investigated the changes in TIL qualities when the ex vivo microenvironment of intact tumor fragments were modulated with checkpoint inhibitors targeting PD-1 and CTLA-4. We found that unmodified TILs from CPI-resistant individuals could be produced, were terminally differentiated, and capable of responding to tumor. Furthermore, we confirmed the specificity of TILs to highly responding tumor antigens and identified the contribution of specific CD39(+)CD69(+) terminally differentiated populations.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Oncology
Lasse Kjaer, Vibe Skov, Morten Kranker Larsen, Tobias Idor Boklund, Morten Andersen, Maria Kefala, Trine A. Knudsen, Christina Schjellerup Eickhardt-Dalboge, Thomas Stiehl, Johanne Gudmand-Hoyer, Jordan Snyder, Morten Holmstrom, Mads H. Andersen, Johnny T. Ottesen, Christina Ellervik, Hans C. Hasselbalch
Summary: The initial diagnosis of overt myeloproliferative neoplasms (MPNs) occurs when symptoms or complications lead to a patient seeking medical attention. In some MPN subgroups like essential thrombocythemia (ET) and myelofibrosis (MF), somatic mutations in the calreticulin gene (CALR) are the drivers of the disease. This study follows a healthy individual with a CALR mutation from initial identification as CALR clonal hematopoiesis of indeterminate potential (CHIP) to the diagnosis of pre-MF, providing insights into pre-diagnostic dynamics that may aid in early diagnosis and intervention in MPN patients.
FRONTIERS IN ONCOLOGY
(2023)
Article
Immunology
Morten Orebo Holmstrom, Morten Andersen, Sofie Traynor, Shamaila Munir Ahmad, Thomas Landkildehus Lisle, Jacob Handlos Grauslund, Vibe Skov, Lasse Kjaer, Johnny T. Ottesen, Morten Frier Gjerstorff, Hans Carl Hasselbalch, Mads Hald Andersen
Summary: CALRmut specific T cells do not increase in the bone marrow after therapeutic cancer vaccination against mutant CALR, possibly due to a high burden of CALRmut cells compared to the number of effector T cells in the peripheral blood.
FRONTIERS IN IMMUNOLOGY
(2023)
Review
Oncology
Hans Carl Hasselbalch, Peter Junker, Vibe Skov, Lasse Kjaer, Trine A. Knudsen, Morten Kranker Larsen, Morten Orebo Holmstroem, Mads Hald Andersen, Christina Jensen, Morten A. Karsdal, Nicholas Willumsen
Article
Biochemistry & Molecular Biology
Mikkel O. Norgard, Philip M. Lund, Nazmie Kalisi, Thomas L. Andresen, Jannik B. Larsen, Stefan Vogel, Per Svenningsen
Summary: Extracellular vesicle (EV) secretion rate is increased by hypoxia-induced reactive oxygen species (ROS) production via the mitochondrial electron transport chain (ETC) and hypoxia-induced factor (HIF)-1 signaling. Stimulation of ETC by dichloroacetic acid (DCA) significantly increases EV secretion, which can be blocked by the antioxidant TEMPO and rotenone, an inhibitor of Complex I in the ETC. Inhibition of Complex III using antimycin A or blocking the mevalonate pathway and tyrosine metabolites with pitavastatin and 4-nitrobenzoate, respectively, enhances ROS-dependent EV secretion. These findings demonstrate that hypoxia-mimetics targeting the ETC can modify EV secretion, and ROS produced by the ETC acts as a potent stimulus for EV secretion.
