Article
Gastroenterology & Hepatology
Edward J. Gane, Hyung Joon Kim, Kumar Visvanathan, Yoon Jun Kim, Anh-Hoa Nguyen, Jeffrey J. Wallin, Diana Y. Chen, Circe McDonald, Priyanka Arora, Susanna K. Tan, Anuj Gaggar, Stuart K. Roberts, Young-Suk Lim
Summary: Selgantolimod was found to be safe and well-tolerated in patients with chronic hepatitis B (CHB), inducing cytokine responses and antiviral immunity. Although some patients experienced adverse events and laboratory abnormalities, they were mild or moderate in severity. Further studies with longer treatment durations are needed to assess efficacy.
Article
Immunology
Manju Sharma, Liang Niu, Xiang Zhang, Shouxiong Huang
Summary: A study found that Mucosal-Associated Invariant T (MAIT) cells provide protection against tuberculous and non-tuberculous mycobacterial infections, but the mechanisms are poorly understood. Comparing the responses of MAIT cells to E. coli and Bacillus Calmette-Guerin (BCG) stimulation, it was observed that BCG induced greater changes in MAIT cell genes, enhancing their survival and cytotoxic capabilities. Therefore, this study suggests that BCG induces cell-mediated effector responses in MAIT cells to combat mycobacterial infections.
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY
(2023)
Article
Immunology
Irene Veneziani, Claudia Alicata, Lorenzo Moretta, Enrico Maggi
Summary: Toll-like receptors (TLRs) are described as homo- or heterodimeric proteins mainly in antigen presenting cells like dendritic cells (DCs), but recent studies have discovered their expression and role also in natural killer (NK) cells. The activation and function of TLRs can be modulated directly or indirectly by TLR agonists. The interplay between DCs and NK cells, mediated by cell-to-cell contact and soluble factors, promotes DC maturation and NK cell activation. Based on this concept, TLR-based immunotherapy targeting the NK-DC axis has been proposed to modulate the tumor microenvironment, improve DC antigen presentation, and enhance NK cell cytotoxicity against tumor cells.
IMMUNOLOGY LETTERS
(2023)
Article
Virology
Sebastian Deschler, Juliane Kager, Johanna Erber, Lisa Fricke, Plamena Koyumdzhieva, Alexandra Georgieva, Tobias Lahmer, Johannes R. Wiessner, Florian Voit, Jochen Schneider, Julia Horstmann, Roman Iakoubov, Matthias Treiber, Christof Winter, Jurgen Ruland, Dirk H. Busch, Percy A. Knolle, Ulrike Protzer, Christoph D. Spinner, Roland M. Schmid, Michael Quante, Katrin Bottcher
Summary: MAIT cells in patients with COVID-19 show high activation and expression of proinflammatory cytokines, while their antibacterial and antiviral function is impaired. The data points towards the importance of MAIT cells in the pathogenesis of COVID-19.
Review
Immunology
Yanmei Li, Jun Du, Wei Wei
Summary: This review discusses the role of mucosal-associated invariant T (MAIT) cells in rheumatic diseases, emphasizing the potential for further research on MAIT cells to inform the development of novel biomarkers and therapeutic approaches in rheumatology.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Multidisciplinary Sciences
Xiaoyu Wang, Yu Chen, Steven Zhang, Jinxia Nancy Deng
Summary: TLR7 and TLR8 play crucial roles in innate immunity and can be therapeutic targets for diseases like infections and cancer. The biological response to small molecule binding differs between TLR7 and TLR8. Through molecular dynamic simulations and binding free energy calculations, it was found that selective agonists were more favorable for TLR7. Van der Waals interactions were identified as the driving force for agonist binding.
Article
Immunology
Xue Wen, Siji Nian, Gang Wei, Pengyuan Kang, Yaqi Yang, Lin Li, Yingchun Ye, Lulu Zhang, Songping Wang, Qing Yuan
Summary: This study evaluated the phenotype and function of circulating mucosal-associated invariant T (MAIT) cells in patients with neutrophilic asthma (NA). The results showed that NA patients had significantly decreased frequency of MAIT cells, altered phenotype, and biased Th17 immune response. The study suggests that MAIT cells could be a potential therapeutic target for NA asthma.
INTERNATIONAL IMMUNOPHARMACOLOGY
(2022)
Article
Oncology
Qian Peng, Renhua Huang, Huiping Wang, Hao Xiao, Yiping Wang, Zhimin Zhai, Zhitao Wang
Summary: This study investigated the immune characteristics of mucosal-associated invariant T cells (MAITs) in patients with acute myeloid leukemia (AML) and found that these cells may play a crucial role in AML pathogenesis and treatment.
CANCER IMMUNOLOGY IMMUNOTHERAPY
(2023)
Article
Immunology
Yasuo Shimizu, Yukiko Horigane-Konakai, Yoshii Ishii, Chie Sugimoto, Hiroshi Wakao
Summary: Mucosal-associated invariant T (MAIT) cells play a crucial role in allergic airway inflammation by suppressing the production of cytokines by group 2 innate lymphoid cells (ILC2s) and inhibiting ILC2 proliferation.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Immunology
Wenjia Qiu, Ning Kang, Yanxu Wu, Yongjun Cai, Li Xiao, Haiyan Ge, Huili Zhu
Summary: MAIT cells in COPD patients exhibit distinct biological functions, producing more IL-17 and less IFN-γ compared to healthy individuals, and are correlated with inflammation levels and lung function. These cells are highly expressed in inflammatory tissues, suggesting a potential role in COPD immunopathology.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Immunology
Lichen Ouyang, Mi Wu, Zhijun Shen, Xue Cheng, Wei Wang, Lang Jiang, Juan Zhao, Yeli Gong, Zhihui Liang, Xiufang Weng, Muqing Yu, Xiongwen Wu
Summary: The study found that the frequency of MAIT cells in peripheral blood of adult CAP patients is lower, with higher expression of CD69 and PD-1, compared to healthy individuals. MAIT-cell frequency is higher in bronchoalveolar lavage fluid of CAP patients, along with higher levels of CD69 and PD-1. The IL-17A/IFN-gamma ratio is positively correlated with MAIT frequency in BALF of CAP patients, suggesting a potential pathogenic role of MAIT cells in CAP.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Pharmacology & Pharmacy
Deepender Kaushik, Juliana T. Granato, Gilson C. Macedo, Paula R. B. Dib, Sakshi Piplani, Johnson Fung, Adilson D. da Silva, Elaine S. Coimbra, Nikolai Petrovsky, Deepak B. Salunke
Summary: The study evaluated the anti-Leishmanial activity of imidazoquinoline-based TLR7/8 agonists. Compounds 2 and 3, as TLR7 agonists, showed promise in inhibiting the growth of L. amazonensis-intracellular amastigotes by inducing the production of free radicals and inflammatory cytokines from macrophages. While these compounds had narrow cytotoxicity windows for macrophages, they could potentially be further developed as less cytotoxic TLR7/8 agonists for anti-Leishmanial drug development.
JOURNAL OF PHARMACY AND PHARMACOLOGY
(2021)
Article
Immunology
Lichen Ouyang, Mi Wu, Juan Zhao, Lang Jiang, Zhijun Shen, Xue Cheng, Wei Wang, Xiongwen Wu, Xiaonian Cao, Xiufang Weng
Summary: This study evaluates the clinical relevance of MAIT cells in blood and tumor tissues of NSCLC patients. The results show a significant decline in the frequency of MAIT cells in lung tumor tissues, which is related to TNM stage. Additionally, tumor-infiltrating MAIT cells exhibit increased levels of exhaustion markers.
INTERNATIONAL IMMUNOPHARMACOLOGY
(2022)
Article
Immunology
Natarajan Ayithan, Lydia Tang, Susanna K. Tan, Diana Chen, Jeffrey J. Wallin, Simon P. Fletcher, Shyam Kottilil, Bhawna Poonia
Summary: TLR8 activation enhances follicular helper T cell function, leading to improved B cell response in chronic hepatitis B infection. TLR8 agonists may promote monocyte-mediated T-FH function and enhance HBV-specific B cell responses, potentially playing a role in achieving HBV functional cure.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Cell Biology
Qiushi Qin, Rui Li, Lan Li, Yue Zhang, Shuwei Deng, Liuluan Zhu
Summary: This study reveals that Blimp-1 regulates the production of multiple pro-inflammatory cytokines by controlling nuclear translocation and transcriptional activity. This finding may offer potential therapeutic strategies for cytokine storm-related diseases.
INFLAMMATION RESEARCH
(2023)
Article
Immunology
Sharon A. Riddler, Michael Para, Constance A. Benson, Anthony Mills, Moti Ramgopal, Edwin DeJesus, Cynthia Brinson, Joshua Cyktor, Jana Jacobs, Dianna Koontz, John W. Mellors, Gregory M. Laird, Terri Wrin, Heena Patel, Susan Guo, Jeffrey Wallin, Jillian Boice, Liao Zhang, Rita Humeniuk, Rebecca Begley, Polina German, Hiba Graham, Romas Geleziunas, Diana M. Brainard, Devi SenGupta
Summary: In a Phase Ib study investigating the effects of vesatolimod in adults with HIV-1, the drug was found to be generally well tolerated and immune stimulation was observed at doses above 4 mg, indicating potential for future combination trials in individuals living with HIV.
CLINICAL INFECTIOUS DISEASES
(2021)
Article
Gastroenterology & Hepatology
Edward J. Gane, Hyung Joon Kim, Kumar Visvanathan, Yoon Jun Kim, Anh-Hoa Nguyen, Jeffrey J. Wallin, Diana Y. Chen, Circe McDonald, Priyanka Arora, Susanna K. Tan, Anuj Gaggar, Stuart K. Roberts, Young-Suk Lim
Summary: Selgantolimod was found to be safe and well-tolerated in patients with chronic hepatitis B (CHB), inducing cytokine responses and antiviral immunity. Although some patients experienced adverse events and laboratory abnormalities, they were mild or moderate in severity. Further studies with longer treatment durations are needed to assess efficacy.
Article
Virology
Minchao Li, Jinfeng Zeng, Ruiting Li, Ziyu Wen, Yanhui Cai, Jeffrey Wallin, Yuelong Shu, Xiangjun Du, Caijun Sun
Summary: Developing a global HCoVs vaccine is crucial in the field of public health with the rapid spread of COVID-19. The novel antigen design with broad coverage has the potential to induce strong CTL responses.
Review
Cell Biology
Arshi Khanam, Paul G. Saleeb, Shyam Kottilil
Summary: Hepatic fibrosis is a complex pathophysiological process involving interactions between various cells and molecular mechanisms that result in liver damage and cell transformation. While several therapeutic approaches exist to inhibit fibrosis, few have advanced from preclinical studies to clinical trials.
Review
Biochemistry & Molecular Biology
Arshi Khanam, Joel V. Chua, Shyam Kottilil
Summary: This review discusses the current knowledge of innate and adaptive immune cell transformations associated with immunopathogenesis and disease outcome in chronic hepatitis B patients.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Cell Biology
Devi SenGupta, Cynthia Brinson, Edwin DeJesus, Anthony Mills, Peter Shalit, Susan Guo, Yanhui Cai, Jeffrey J. Wallin, Liao Zhang, Rita Humeniuk, Rebecca Begley, Romas Geleziunas, John Mellors, Terri Wrin, Norman Jones, Jeffrey Milush, April L. Ferre, Barbara L. Shacklett, Greg M. Laird, Brian Moldt, Elena Vendrame, Diana M. Brainard, Moti Ramgopal, Steven G. Deeks
Summary: TLR7 agonist vesatolimod, when combined with ART, showed potential to delay viral rebound in HIV-1-infected controllers by reducing intact proviral DNA levels at the end of treatment. Further larger clinical studies are needed to evaluate the efficacy of vesatolimod-based combination therapies for long-term control of HIV infection.
SCIENCE TRANSLATIONAL MEDICINE
(2021)
Article
Virology
Jennifer Wellington, Andrew Ma, Shyam Kottilil, Bharath Ravichandran, Jennifer Husson, David Bruno, Eleanor Wilson
Summary: Liver transplantation for HCV-related disease has the lowest five-year graft survival, and graft failure due to accelerated fibrosis is common. Timing of HCV treatment with direct-acting antiviral agents remains unknown, but early treatment may prevent accumulation of HCV-related disease. Despite treatment before or after transplantation, there was no significant difference in the risk of greater than minimal fibrosis one year after transplant.
Article
Oncology
Kyung W. Song, Kyle A. Edgar, Emily J. Hanan, Marc Hafner, Jason Oeh, Mark Merchant, Deepak Sampath, Michelle A. Nannini, Rebecca Hong, Lilian Phu, William F. Forrest, Eric Stawiski, Stephen Schmidt, Nicholas Endres, Jane Guan, Jeffrey J. Wallin, Jonathan Cheong, Emile G. Plise, Gail D. Lewis Phillips, Laurent Salphati, Timothy P. Heffron, Alan G. Olivero, Shiva Malek, Steven T. Staben, Donald S. Kirkpatrick, Anwesha Dey, Lori S. Friedman
Summary: The PI3K inhibitors GDC-0077 and taselisib have a unique mechanism of action by degrading mutant p110a protein, leading to more potent inhibition of mutant PI3K pathway signaling and cell viability, and better maintenance of prolonged pathway suppression.
Article
Virology
Shikha Shrivastava, Shyam Kottilil, Kenneth E. Sherman, Henry Masur, Lydia Tang
Summary: In patients coinfected with HIV and HCV, there is a higher number of CCR5+ T cells in the liver, which are functionally proinflammatory and profibrogenic, leading to accelerated fibrosis. Targeting CCR5 could be a potential therapeutic strategy for ameliorating liver fibrosis in these patients.
Article
Pharmacology & Pharmacy
Rajbharan Yadav, Siddharth Sukumaran, Tanja S. Zabka, Jinze Li, Amy Oldendorp, Gary Morrow, Arthur Reyes, Melissa Cheu, Jessica Li, Jeffrey J. Wallin, Siao Tsai, Laura Sun, Peiyin Wang, Diego Ellerman, Christoph Spiess, Andy Polson, Eric G. Stefanich, Amrita Kamath, Meric A. Ovacik
Summary: The study focuses on the impact of CD3 binding affinity on the pharmacokinetics of T cell-dependent bispecific antibodies. The results demonstrate that CD3 binding affinity affects the clearance rate of the antibody and may be related to the internalization rate of CD79b and the binding ability of CD3.
Article
Gastroenterology & Hepatology
Edward J. Gane, P. Rod Dunbar, Anna E. Brooks, Fangqiu Zhang, Diana Chen, Jeffrey J. Wallin, Nicholas van Buuren, Priyanka Arora, Simon P. Fletcher, Susanna K. Tan, Jenny C. Yang, Anuj Gaggar, Shyamasundaran Kottilil, Lydia Tang
Summary: Selgantolimod treatment showed positive effects on hepatitis B surface antigen, but only a few patients achieved the primary efficacy endpoint. The common adverse events during treatment included nausea, upper respiratory tract infection, and vomiting. Overall, this treatment approach showed potential in a small proportion of patients.
JOURNAL OF HEPATOLOGY
(2023)
Review
Biochemistry & Molecular Biology
Arshi Khanam, Shyam Kottilil
Summary: The incidence of liver cancer, mainly hepatocellular carcinoma (HCC), is increasing. HCC is influenced by the tumor microenvironment and immune mechanisms play a critical role in its development, progression, and metastasis. The initial inflammatory tumor immune microenvironment transitions to an immunosuppressive state, contributing to tumor immune escape. Despite advancements in systemic therapy, HCC prognosis remains poor due to drug resistance, recurrence, and metastasis. Current focus is on new immunotherapeutic strategies to induce effective HCC-specific immune responses and overcome treatment hurdles. This review provides an update on the immunological mechanisms associated with HCC and discusses potential advancements in immunotherapies for HCC treatment.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Medicine, Research & Experimental
David Z. Pan, Pamela M. Odorizzi, Andre Schoenichen, Mazin Abdelghany, Shuguang Chen, Anu Osinusi, Scott D. Patterson, Bryan Downie, Kavita Juneja, Jeffrey J. Wallin
Summary: This study assessed the impact of RDV treatment on biomarkers in COVID-19 patients. The findings indicate that RDV treatment can accelerate the improvement of multiple biomarkers associated with COVID-19 severity, leading to better clinical outcomes.
COMMUNICATIONS MEDICINE
(2023)
Article
Gastroenterology & Hepatology
Nicholas van Buuren, Ricardo Ramirez, Scott Turner, Diana Chen, Vithika Suri, Abhishek Aggarwal, Christina Moon, Sam Kim, Dmytro Kornyeyev, Nam Bui, Neeru Bhardwaj, Henry Ly Chan, Patrick Marcellin, Maria Buti, Jeffrey Wallin, Anuj Gaggar, Simon P. Fletcher, Lauri Diehl, Li Li, Hongmei Mo, Becket Feierbach
Summary: By analyzing liver biopsies from patients with chronic HBV infection using RNA-Seq and a custom multiplex immunofluorescence panel, two distinct liver immune microenvironments were identified as immune high and immune low. Patients with immune high status exhibited elevated immune pathways and increased presence of immune cells.