Review
Physiology
Corina Bello, Paul Philipp Heinisch, Maks Mihalj, Thierry Carrel, Markus M. Luedi
Summary: IDO is a rate-limiting enzyme in the tryptophan catabolism pathway, playing a crucial role in immune modulation and the pathogenesis of various diseases. Its involvement has been extensively studied in autoimmune processes and highly malignant cancers, with potential as a predictive biomarker and therapeutic target in immune-mediated diseases. Additionally, IDO shows promise as a biomarker in the pre-operative setting for decision-making and treatment of surgical patients experiencing trauma-induced stress.
FRONTIERS IN PHYSIOLOGY
(2021)
Review
Biochemistry & Molecular Biology
Leila Sawada, Antonio Carlos Rosario Vallinoto, Igor Brasil-Costa
Summary: EBV is an oncovirus associated with various types of cancer, with the reason for cancer development in only some infected individuals still unknown. EBV-associated cancers are more aggressive and resistant to treatment compared to EBV-negative cancers, making monoclonal antibodies targeting immune checkpoints a potential therapy.
Review
Pharmacology & Pharmacy
Ana Dolsak, Stanislav Gobec, Matej Sova
Summary: This review discusses the key step of tryptophan metabolism and the importance of relevant enzymes in pathological conditions. In recent years, many inhibitors targeting these enzymes have been developed, and these inhibitors have entered clinical trials.
PHARMACOLOGY & THERAPEUTICS
(2021)
Article
Oncology
Xinyu Qu, Yumeng Wang, Qian Jiang, Tingting Ren, Chenyan Guo, Keqin Hua, Junjun Qiu
Summary: This study investigates the mechanism of cervical cancer immune remodeling and explores the potential therapeutic targets. The research suggests that a combination treatment targeting IDO1 and ICB agent could improve the therapeutic efficacy of current cervical cancer immunotherapies.
CANCER COMMUNICATIONS
(2023)
Article
Chemistry, Multidisciplinary
Nirmalya Pradhan, Nasim Akhtar, Barnali Nath, Jorge Pena-Garcia, Anjali Gupta, Horacio Perez-Sanchez, Sachin Kumar, Debasis Manna
Summary: Quinine derivatives effectively inhibit the activity of IDO1 by competing with heme, providing a potential avenue for immunotherapy-based drug discovery strategies.
CHEMICAL COMMUNICATIONS
(2021)
Article
Chemistry, Medicinal
Arina Kozlova, Leopold Thabault, Maxime Liberelle, Simon Klaessens, Julien R. C. Prevost, Caroline Mathieu, Luc Pilotte, Vincent Stroobant, Benoit Van den Eynde, Raphael Frederick
Summary: In this study, a new scaffold of TDO2 inhibitors, 6-(1H-indol-3-yl)-benzotriazole, was developed through rational design, leading to the synthesis of stable compounds with nanomolar cellular potency. The rigidification of the initial scaffold provided a better understanding of the structural modulations inside the active site of hTDO2.
JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Review
Oncology
Yu Yao, Heng Liang, Xin Fang, Shengnan Zhang, Zikang Xing, Lei Shi, Chunxiang Kuang, Barbara Seliger, Qing Yang
Summary: IDO1, a heme-containing enzyme, plays a crucial role in the kynurenine pathway of tryptophan metabolism, with implications in immunity and neuronal function. Despite potential applications in cancer and neurodegenerative diseases, cautionary notes from clinical trials indicate a need for better understanding of IDO1 inhibition mechanisms.
JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH
(2021)
Article
Oncology
Liang Shi, Rui Duan, Qiong Jia, Wenyu Wu, Jianming Zhou, Shaohua Li, Hao Zhang, Xue Xue
Summary: This study found that radioiodine therapy can alter indoleamine 2,3-dioxygenase (IDO) activity in patients with distant metastatic differentiated thyroid cancer (dmDTC). IDO activity is associated with treatment response, progression-free survival, and overall survival in dmDTC patients. Serum IDO biomarker levels may be used to select dmDTC patients likely to benefit from radioiodine therapy.
FRONTIERS IN ONCOLOGY
(2022)
Article
Oncology
Rui Qin, Chen Zhao, Chen-Ji Wang, Wei Xu, Jian-Yuan Zhao, Yan Lin, Yi-Yuan Yuan, Peng-Cheng Lin, Yao Li, Shimin Zhao, Yan Huang
Summary: This study demonstrated that IDO inhibitors activate CD8(+) T cells by increasing tryptophan levels and consequently downregulating PD-1 expression. Tryptophan and IDO inhibitors both potentiate CD8(+) T cells to induce apoptosis of cancer cells through different mechanisms, suggesting a potential synergistic effect in anticancer treatments.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2021)
Review
Immunology
Georgia Wells, Paul T. Kennedy, Lekh N. Dahal
Summary: Studies suggest that IDO expression in AML is associated with poor prognosis and correlates positively with Treg induction. Pharmacological inhibition of IDO may hold promise for the treatment of AML.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Chemistry, Medicinal
Ke Wang, Long-Hao Song, Qiao-Ling Liang, Ye Zhang, Xian-Li Ma, Qi Wang, Hui-Yong Zhang, Cai-Na Jiang, Jian-Hua Wei, Ri-Zhen Huang
Summary: A series of chromone-oxime derivatives containing piperazine sulfonamide moieties were synthesized and evaluated as IDO1 inhibitors. Compound 10m exhibited good inhibitory activity against IDO1. It was found that 10m directly interacted with IDO1 and formed key interactions. These chromone-oxime derivatives containing sulfonamide moieties might be potential IDO1 inhibitors for the development of new antitumor agents.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Cell Biology
Raghavan Chinnadurai, Amanda Paige Porter, Mihir Patel, Ariel Joy Lipat, Mathews H. Forsberg, Devi Rajan, Peiman Hematti, Christian M. Capitini, Charles Bruker
Summary: B7 family proteins and tryptophan degrading enzymes play crucial roles in tumor immune evasion. The interactions between tumor cells, stromal cells, and immune cells contribute to the development of an immunosuppressive tumor microenvironment. IFN-γ activated MSCs exhibit superior protection of HepG2 cells from PBMC mediated lysis and blockade of IFN-γ driven IDO activity in MSCs could be a potential immunotherapeutic strategy for hepatocellular carcinoma regression.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Chemistry, Medicinal
Juyoung Jung, Hongchul Yoon, Te-ik Sohn, Kyusic Jang, Yeongran Yoo, Ilji Jeong, Jae Eui Shin, Jin Hee Lee, Jihyae Ann, Jeewoo Lee
Summary: Through a structure-activity relationship study, the N-3-bromophenyl derivative 19 was identified as the most potent inhibitor of IDO1, with an IC50 value of 0.44 μM. Molecular modeling revealed that interactions with heme iron, halogen bonding with Cys129, and hydrophobic interactions were crucial for the high potency of compound 19.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2021)
Review
Oncology
Yu Fujiwara, Shumei Kato, Mary K. Nesline, Jeffrey M. Conroy, Paul DePietro, Sarabjot Pabla, Razelle Kurzrock
Summary: Strategies to overcome immunosuppression in the tumor microenvironment, such as IDO1 inhibition, have been explored to address resistance to immune checkpoint blockade. These strategies have shown promising results in preclinical studies and early-phase clinical trials. However, some clinical trials have yielded disappointing results, dampening enthusiasm for IDO inhibitors. Additional potential targets, such as the aryl hydrocarbon receptor and tryptophan 2,3-dioxygenase, have been proposed to enhance clinical effectiveness. The expression level of IDO1 varies among tumors and patients, highlighting the importance of patient selection based on IDO1 expression levels in clinical trials.
CANCER TREATMENT REVIEWS
(2022)
Article
Immunology
Bing Liu, Xu He, Yong Wang, Jian-Wen Huang, You-Bing Zheng, Yong Li, Li-Gong Lu
Summary: Gamma delta T cells are unique immune cells that play a role in cancer progression, particularly in gastric and breast cancers. China has shown the highest productivity and citations in international research collaboration. The cytokines IL-17 and IL-2 are most commonly associated with gamma delta T cells and have different roles in various malignancies.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Oncology
Eva Ellebaek, Aimilia Schina, Henrik Schmidt, Charlotte Aaquist Haslund, Lars Bastholt, Inge Marie Svane, Marco Donia
Summary: This study found that initiation of immunotherapy in summer is associated with prolonged survival in patients with BRAF wild-type melanoma in Denmark.
PIGMENT CELL & MELANOMA RESEARCH
(2023)
Editorial Material
Infectious Diseases
Mads Hald Andersen
Article
Medicine, General & Internal
Nicklas Juel Spindler, Gitte Fredberg Persson, Susann Theile, Dorte Lisbeth Nielsen, Estrid Hogdall, Gina Al-Farra, Helle Westergren Hendel, Torben Lorentzen, Inge Marie Svane, Henriette Lindberg, Rikke Lovendahl Eefsen
Summary: This study aims to investigate the efficacy of combining SBRT and CPI treatment in patients with mCRPC. A total of 80 evaluable patients who have progressed after multiple lines of treatment will be enrolled and receive ipilimumab and nivolumab combination therapy, with some patients also receiving SBRT. The primary endpoints are objective response rate and PSA response rate, and secondary endpoints include safety, radiographic progression-free survival, clinical benefit rate, duration of response, PSA-progression-free survival beyond 12 weeks, quality of life, and overall survival. The results will be published in an international peer-reviewed journal.
Article
Oncology
Amalie Valentin, Anne Kirstine Hundahl Moller, Jesper Andreas Palshof, Bo Broberg, Eva Gravesen, Inge Marie Svane, Ditte Hansen
Summary: This study aimed to describe the incidence and causes of AKI in patients treated with immune checkpoint inhibitors. The study showed that 16% of malignant melanoma patients and 25% of metastatic renal cell carcinoma patients developed AKI. Some of these cases may be related to immune checkpoint inhibitors or the use of proton pump inhibitors.
Letter
Gastroenterology & Hepatology
Emilie Dahl, Osama Abed, Jorgen Agnholt, Jacob Bjerrum, Anders Dige, Jens Kjeldsen, Inge Svane, Marco Donia, Jakob Seidelin
Summary: This article is linked to Dahl et al papers. To view these articles, visit...
ALIMENTARY PHARMACOLOGY & THERAPEUTICS
(2023)
Article
Oncology
Neel Maria Helvind, Marie Brinch-Moller Weitemeyer, Annette Hougaard Chakera, Helle Westergren Hendel, Eva Ellebaek, Inge Marie Svane, Mette Wanscher Kjaerskov, Sophie Bojesen, Helle Skyum, Soren Kjaer Petersen, Lars Bastholt, Christoffer Johansen, Pernille Envold Bidstrup, Lisbet Rosenkrantz Holmich
Summary: This study aimed to determine the impact of surveillance with routine FDG PET-CT on hazard, cumulative incidence, and absolute risk of overall, locoregional, and distant recurrence detection in patients with stage IIB to IIID cutaneous melanoma. The study found that patients with stage IIB to IIID melanoma followed with routine FDG PET-CT had a 51% increased hazard of distant recurrence detection within the first two years of surveillance.
ANNALS OF SURGICAL ONCOLOGY
(2023)
Article
Infectious Diseases
Moises Alberto Suarez-Zdunek, Sunil Kumar Saini, Christian Ross Pedersen, Sebastian Rask Hamm, Annemette Hald, Allan Rasmussen, Jens Georg Hillingso, Sine Reker Hadrup, Susanne Dam Nielsen
Summary: This study aims to explore the cellular immune response against CMV and VZV infections in liver transplant recipients and identify potential risk factors for infection. Through an epidemiological substudy and an immunological substudy, the incidence and clinical risk factors for CMV and VZV infections will be determined, and the frequency, T cell receptor sequences, and phenotypic characteristics of CMV- and VZV-specific T cells will be examined. The study has the potential to develop a prediction model and proof-of-concept for adoptive T cell therapy against CMV and VZV to reduce the burden and consequence of infections in liver transplant recipients.
BMC INFECTIOUS DISEASES
(2023)
Editorial Material
Immunology
Mads Hald Andersen
SEMINARS IN IMMUNOPATHOLOGY
(2023)
Article
Biology
Helle Rus Povlsen, Amalie Kai Bentzen, Mohammad Kadivar, Leon Eyrich Jessen, Sine Reker Hadrup, Morten Nielsen, K. Christopher Garcia
Summary: Novel single-cell-based technologies enable high-throughput matching of T cell receptor (TCR) sequences with their cognate peptide-MHC recognition motif. A data-driven method called ITRAP is proposed to filter out likely artifacts and generate large sets of TCR-pMHC sequence data with high specificity and sensitivity. This approach has been validated in virus-specific T cell responses across multiple healthy donors.
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
Oncology
Rasmus Erik Johansson Mortensen, Morten Orebo Holmstrom, Thomas Landkildehus Lisle, Jane P. Hasselby, Gro L. Willemoe, Ozcan Met, Inge Marie Svane, Julia Johansen, Dorte L. Nielsen, Inna M. Chen, Mads Hald Andersen
Summary: This study investigated the significance of TGF-beta-specific T-cell immunity in patients with pancreatic cancer treated with ICI combined with radiotherapy. The results showed that patients with a strong TGF-beta-specific immune response had longer progression-free and overall survival compared to those with a weak or no response. It was also found that TGF-beta-specific T cells could recognize and enhance immune responses. Thus, combining TGF-beta vaccination with ICI/radiotherapy may benefit patients with pancreatic cancer.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2023)
Article
Oncology
Cathrine Lund Lorentzen, Julie Westerlin Kjeldsen, Eva Ehrnrooth, Mads Hald Andersen, Inge Marie Svane
Summary: Summary: This study presented the long-term follow-up results of the IDO/PD-L1 vaccine and nivolumab combination therapy in cohort A, showing promising efficacy with high overall response rates and durable responses. However, cohort B did not show significant clinical effects.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2023)
Article
Infectious Diseases
Sebastian Rask Hamm, Sunil Kumar Saini, Annemette Hald, Anna V. Vaaben, Natasja Wulff Pedersen, Moises Alberto Suarez-Zdunek, Zitta Barrella Harboe, Helle Bruunsgaard, Isik Somuncu Johansen, Carsten Schade Larsen, Claus Bistrup, Henrik Birn, Soren Schwartz Sorensen, Sine Reker Hadrup, Susanne Dam Nielsen
Summary: This study aims to characterize the immune response to RZV vaccination in kidney transplant candidates and recipients. The study will provide new knowledge and potentially enhance preventive strategies against herpes zoster in a population at increased risk.
BMC INFECTIOUS DISEASES
(2023)