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
Pharmacology & Pharmacy
Dan Yang, Yinxian Chen, Zhen Ning Tony He, Yichen Wang, Chenghui Ke, Yi Luo, Sun Wang, Qichao Ma, Mengjie Chen, Qing Yang, Ziming Zhang
Summary: This study found that the immunosuppressive enzyme IDO1 is highly expressed in osteosarcoma tissues and is related to immune tolerance and progression of the tumor. Experimental results showed that IDO1 significantly affects exosome-derived miRNA subsets from osteosarcoma cells. The key miRNA hsa-miR-23a-3p involved in the progression of osteosarcoma was identified. Targeting IDO1-mediated hsa-miR-23a-3p could be a potential therapeutic strategy for osteosarcoma treatment.
FRONTIERS IN PHARMACOLOGY
(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)
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)
Review
Biochemistry & Molecular Biology
Seyed-Alireza Esmaeili, Jafar Hajavi
Summary: This review discusses the mechanism of immune response regulation through manipulating tryptophan metabolism. Studies suggest that the IDO-kynurenine pathway may play different roles in regulating Th2 cells and Th1 cells immune responses.
MOLECULAR BIOLOGY REPORTS
(2022)
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
Dentistry, Oral Surgery & Medicine
Cristina Cunha Villar, Anna Dongari-Bagtzoglou
Summary: The oral microbiota plays a key role in maintaining a healthy oral cavity, and the development of oral candidiasis is influenced by dysbiosis and disturbances in the host's immune system. Various factors, including medications, host genetics, and microbial interactions, can disrupt the oral microbiota and increase the risk of oral candidiasis.
PERIODONTOLOGY 2000
(2021)
Review
Chemistry, Medicinal
Rahul Singh, Deepak B. Salunke
Summary: IDO1 enzyme catalyzes the initial step of kynurenine pathway and is implicated in immune modulation, antioxidation, and cancer progression. Overexpression of IDO1 plays a pivotal role in immune evasion and cancer development. Research and development of IDO1 inhibitors holds significant potential in immunotherapy and disease treatment.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Engineering, Biomedical
Yixuan Guo, Yu Liu, Wei Wu, Daishun Ling, Qiao Zhang, Peng Zhao, Xi Hu
Summary: This article will discuss different types of IDO inhibitors and relevant clinical trials, especially feasible combined therapeutic modalities. In addition, it will also review cutting-edge nanomedicines that combine IDO inhibitors with other therapeutic modalities to effectively enhance the effectiveness of cancer therapy. Finally, the prospects of IDO inhibitors in clinical application and potential breakthroughs will be briefly discussed.
Article
Microbiology
Thiara Manuele Alves de Souza, Caroline Fernandes-Santos, Jessica Araujo da Paixao de Oliveira, Larissa Cristina Teixeira Tome, Victor Edgar Fiestas-Solorzano, Priscila Conrado Guerra Nunes, Gabriel Macedo Costa Guimaraes, Juan Camilo Sanchez-Arcila, Iury Amancio Paiva, Luis Jose de Souza, Paulo Vieira Damasco, Valber da Silva Frutuoso, Manoela Heringer, Luzia Maria De Oliveira-Pinto, Roberta Olmo Pinheiro, Flavia Barreto dos Santos, Elzinandes Leal de Azeredo
Summary: This study evaluated the activity of IDO-1 and the patterns of cytokines/chemokines in CHIKV patients. It was found that IDO-1 activity increased during the early acute phase of infection and decreased in the chronic phase. In the acute phase, concentrations of TNF-alpha, IL-6, IFN-gamma, CCL2/MCP-1, and CXCL10/IP-10 were increased. In the chronic phase, concentrations of CCL4/MIP-1 beta were increased, especially in patients with arthritis.
Article
Chemistry, Medicinal
Kai Tang, Bo Wang, Bin Yu, Hong-Min Liu
Summary: Indoleamine 2,3-dioxygenase 1 (IDO1) is an important immunosuppressive enzyme in cancer therapy. Multiple IDO1 inhibitors have entered clinical trials, and PROTAC-based degraders also show promise for cancer treatment.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
Daojing Yan, Jiakun Xu, Xiang Wang, Jiaxing Zhang, Gang Zhao, Yingwu Lin, Xiangshi Tan
Summary: This study systematically investigated the SAR405838 analogs as potential IDO inhibitors for cancer immunotherapy. The results showed that inhibitor 3 exhibited the highest IDO1 inhibitory activity among all inhibitors and demonstrated effective inhibition in MCF-7 cancer cells.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
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
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)
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
Microbiology
Patricia Alves de Castro, Clara Valero, Jessica Chiaratto, Ana Cristina Colabardini, Lakhansing Pardeshi, Lilian Pereira Silva, Fausto Almeida, Marina Campos Rocha, Roberto Nascimento Silva, Iran Malavazi, Wenyue Du, Paul S. Dyer, Matthias Brock, Flavio Vieira Loures, Koon Ho Wong, Gustavo H. Goldman
Summary: The study revealed the crucial role of the NsdC transcription factor in Aspergillus fumigatus, not only in sexual reproduction and growth regulation, but also in response to calcium stress, cell wall organization, virulence, and host immune recognition. The deletion of nsdC resulted in changes in expression of over 620 genes, indicating its involvement in multiple signaling and metabolic pathways beyond its initially known functions.
Article
Immunology
Juliana de Melo Batista dos Santos, Camila Pereira Soares, Fernanda Rodrigues Monteiro, Ralyria Mello, Jonatas Bussador do Amaral, Andressa Simoes Aguiar, Mariana Pereira Soledade, Carolina Sucupira, Milena De Paulis, Juliana Bannwart Andrade, Flavia Jaqueline Almeida, Marco Aurelio Palazzi Safadi, Luciana Becker Mau, Jamile Menezes Brasil, Theresa Ramalho, Flavio Loures, Rodolfo Paula Vieira, Edison Luiz Durigon, Danielle Bruna Leal de Oliveira, Andre Luis Lacerda Bachi
Summary: The study found higher levels of specific-SIgA for SARS-CoV-2 and cytokines (IFN-beta and IFN-gamma) in the airways mucosa of COVID-19 patients. IL-12p70 levels were observed to be increased in the group with other viruses, and significant differences were found in the immune responses of airway mucosa among different groups of patients with or without SARS-CoV-2 infection.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Medicine, Research & Experimental
Carolina Manganeli Polonio, Carla Longo de Freitas, Marilia Garcia de Oliveira, Cristiano Rossato, Wesley Nogueira Brandao, Nagela Ghabdan Zanluqui, Lilian Gomes de Oliveira, Luiza Ayumi Nishiyama Mimura, Maysa Braga Barros Silva, Vera Lucia Garcia Calich, Marcelo Gil Nisenbaum, Silvio Halpern, Lucila Evangelista, Mariangela Maluf, Paulo Perin, Carlos Eduardo Czeresnia, Jean Pierre Schatzmann Peron
Summary: The research demonstrates the suppressive activity of murine endometrial-derived MSCs on EAE by modulating Th1, Th17 lymphocytes, and IL-10-secreting T CD4(+) cells. The mechanism relies on the IDO-kynurenines-Aryl hydrocarbon receptor (AhR) axis.
Article
Immunology
Joes Nogueira-Neto, Flavio V. Loures, Alessandra S. Schanoski, David A. G. Andrade, Michelangelo B. Gonzatti, Tania A. Costa, Bruno C. Vivanco, Patricia Xander, Daniela S. Rosa, Vera L. G. Calich, Alexandre C. Keller
Summary: iNKT cells play a crucial role in protective immunity against P. brasiliensis infection by enhancing macrophage oxidative burst and controlling fungal growth. Activation of iNKT cells with exogenous ligand alpha-galactosylceramide can improve host resistance to fungal infection.
JOURNAL OF IMMUNOLOGY RESEARCH
(2021)
Article
Immunology
Eliseu F. de Araujo, Flavio V. Loures, Nycolas W. Preite, Claudia Feriotti, Nayane A. L. Galdino, Tania A. Costa, Vera L. G. Calich
Summary: This study demonstrated the modulation of pathogen loads and immune response in pulmonary paracoccidioidomycosis by AhR ligands, with different AhR agonists and antagonists affecting host response differently. Further research is needed to determine the potential use of these compounds as adjuvant therapy for this fungal infection.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Medicine, Research & Experimental
Paula P. Freire, Alexandre H. C. Marques, Gabriela C. Baiocchi, Lena F. Schimke, Dennyson L. M. Fonseca, Ranieri C. Salgado, Igor S. Filgueiras, Sarah M. S. Napoleao, Desiree R. Placa, Karen T. Akashi, Thiago Dominguez Crespo Hirata, Nadia El Khawanky, Lasse M. Giil, Gustavo Cabral-Miranda, Robson F. Carvalho, Luis Carlos S. Ferreira, Antonio Condino-Neto, Helder Nakaya, Igor Jurisica, Hans D. Ochs, Niels Olsen Saraiva Camara, Vera Lucia G. Calich, Otavio Cabral-Marques
Summary: The COVID-19 fatality rate varies by sex and age, with female and young SARS-CoV-2 patients showing a stronger immune response and a closer relationship in gene expression compared to male and elderly patients. The association between upregulated cytokine/chemokine and downregulated neutrophil-related genes is marked by a strongly correlated interferome network. Female patients exhibit reduced transcriptional levels of key proinflammatory/neutrophil-related genes, suggesting protective mechanisms against inflammatory damage.
Article
Biochemistry & Molecular Biology
Gloria Gallo, Uilla Barcick, Camila Coelho, Murilo Salardani, Mauricio F. Camacho, Daniela Cajado-Carvalho, Flavio V. Loures, Solange M. T. Serrano, Leon Hardy, Andre Zelanis, Martin Wurtele
Summary: The main protease Mpro of SARS-CoV-2 is an important drug target and has been linked to the pathogenicity of the virus. By combining proteomics and MM/PBSA modeling analysis, valuable insights into the specificity of Mpro can be obtained, opening up new perspectives for the development of peptidomimetic drugs against COVID-19 and diagnostic tools.
Article
Immunology
Alessandra Soares-Schanoski, Natalie Sauerwald, Carl W. Goforth, Sivakumar Periasamy, Dawn L. Weir, Stephen Lizewski, Rhonda Lizewski, Yongchao Ge, Natalia A. Kuzmina, Venugopalan D. Nair, Sindhu Vangeti, Nada Marjanovic, Antonio Cappuccio, Wan Sze Cheng, Sagie Mofsowitz, Clare M. Miller, Xuechen B. Yu, Mary-Catherine George, Elena Zaslavsky, Alexander Bukreyev, Olga G. Troyanskaya, Stuart C. Sealfon, Andrew G. Letizia, Irene Ramos
Summary: Research has shown that asymptomatic and mild symptomatic COVID-19 infections in young adults have similar viral loads and specific antibody responses, but there are differences in inflammatory protein profiles. Some analytes in asymptomatic infections are associated with tissue repair and may contribute to symptom control.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Cell Biology
Lena F. Schimke, Alexandre H. C. Marques, Gabriela Crispim Baiocchi, Caroline Aliane de Souza Prado, Dennyson Leandro M. Fonseca, Paula Paccielli Freire, Desiree Rodrigues Placa, Igor Salerno Filgueiras, Ranieri Coelho Salgado, Gabriel Jansen-Marques, Antonio Edson Rocha Oliveira, Jean Pierre Schatzmann Peron, Gustavo Cabral-Miranda, Jose Alexandre Marzagao Barbuto, Niels Olsen Saraiva Camara, Vera Lucia Garcia Calich, Hans D. Ochs, Antonio Condino-Neto, Katherine A. Overmyer, Joshua J. Coon, Joseph Balnis, Ariel Jaitovich, Jonas Schulte-Schrepping, Thomas Ulas, Joachim L. Schultze, Helder I. Nakaya, Igor Jurisica, Otavio Cabral-Marques
Summary: Severe COVID-19 patients show similarities with other hyperinflammatory conditions, such as HLH, in terms of clinical and laboratory features. This study highlights the shared immunological pathways and neutrophil-mediated immune responses between COVID-19 and HLH. Dysregulated neutrophil-associated genes and proteins are observed in COVID-19 patients admitted to the ICU, suggesting a generalized hyperinflammatory state. These findings provide potential therapeutic targets for intervention.
Article
Cell Biology
Claudia Feriotti, Joana Sa-Pessoa, Ricardo Calderon-Gonzalez, Lili Gu, Brenda Morris, Ryoichi Sugisawa, Jose L. Insua, Michael Carty, Amy Dumigan, Rebecca J. Ingram, Adrien Kissenpfening, Andrew G. Bowie, Jose A. Bengoechea
Summary: Klebsiella pneumoniae uses SARM1 protein to counteract host immunity and regulate inflammation and MAP kinase activation. Inhibiting SARM1 may be beneficial for treating Klebsiella infections.
Article
Biochemistry & Molecular Biology
Natalie Sauerwald, Zijun Zhang, Irene Ramos, Venugopalan D. Nair, Alessandra Soares-Schanoski, Yongchao Ge, Weiguang Mao, Hala Alshammary, Ana S. Gonzalez-Reiche, Adriana van de Guchte, Carl W. Goforth, Rhonda A. Lizewski, Stephen E. Lizewski, Mary Anne S. Amper, Mital Vasoya, Nitish Seenarine, Kristy Guevara, Nada Marjanovic, Clare M. Miller, German Nudelman, Megan A. Schilling, Rachel S. G. Sealfon, Michael S. Termini, Sindhu Vangeti, Dawn L. Weir, Elena Zaslavsky, Maria Chikina, Ying Nian Wu, Harm Van Bakel, Andrew G. Letizia, Stuart C. Sealfon, Olga G. Troyanskaya
Summary: Male individuals are at a higher risk of severe SARS-CoV-2 infection. This study investigated SARS-CoV-2 infection in a cohort of young adult US Marine recruits and found sex differences in symptoms, viral load, gene expression, RNA splicing, and proteomic signatures. Females exhibited stronger antiviral innate immunity, which plays a causal role in the different responses to SARS-CoV-2 infection based on sex.
Article
Biochemistry & Molecular Biology
Assaf Magen, Pauline Hamon, Nathalie Fiaschi, Brian Y. Soong, Matthew D. Park, Raphael Mattiuz, Etienne Humblin, Leanna Troncoso, Darwin D'souza, Travis Dawson, Joel Kim, Steven Hamel, Mark Buckup, Christie Chang, Alexandra Tabachnikova, Hara Schwartz, Nausicaa Malissen, Yonit Lavin, Alessandra Soares-Schanoski, Bruno Giotti, Samarth Hegde, Giorgio Ioannou, Edgar Gonzalez-Kozlova, Clotilde Hennequin, Jessica Le Berichel, Zhen Zhao, Stephen C. Ward, Isabel Fiel, Baijun Kou, Michael Dobosz, Lianjie Li, Christina Adler, Min Ni, Yi Wei, Wei Wang, Gurinder S. Atwal, Kunal Kundu, Kamil J. Cygan, Alexander M. Tsankov, Adeeb Rahman, Colles Price, Nicolas Fernandez, Jiang He, Namita T. Gupta, Seunghee Kim-Schulze, Sacha Gnjatic, Ephraim Kenigsberg, Raquel P. Deering, Myron Schwartz, Thomas U. Marron, Gavin Thurston, Alice O. Kamphorst, Miriam Merad
Summary: The response to anti-PD-1 in hepatocellular carcinoma patients is associated with the expansion of CXCL13(+)CD4(+) helper T cells and effector-like CD8(+) T cells, as well as the presence of dendritic cells enriched in maturation and regulatory molecules. Tumors rich in T cells often fail to respond to immune checkpoint blockade, but the clonal expansion of specific T cell subsets correlates with response to treatment. The interaction between Progenitor CD8(+) T cells, CXCL13(+) T-H cells, and mregDC plays a role in controlling the differentiation of tumor-specific exhausted CD8(+) T cells following immune checkpoint blockade.
Article
Cell Biology
Marcin Baran, Claudia Feriotti, Aoife McGinley, Simon R. Carlile, Zhaozhao Jiang, Ricardo Calderon-Gonzalez, Amy Dumigan, Joana Sa-Pessoa, Caroline E. Sutton, Jay Kearney, Rachel M. McLoughlin, Kingston H. G. Mills, Katherine A. Fitzgerald, Jose A. Bengeochea, Andrew G. Bowie