Article
Immunology
Jan-Hendrik Schroeder, Katrin Meissl, Dominika Hromadova, Jonathan W. Lo, Joana F. Neves, Jane K. Howard, Helena Helmby, Nick Powell, Birgit Strobl, Graham M. Lord
Summary: T-bet deficient mice show an increase in ILC3 cellularity but do not have a greater risk of developing spontaneous colitis. T-bet appears to control the number of ILC3 cells, but does not drive a pathogenic role of ILC3 in mice with a conventional specific pathogen-free microbiota.
FRONTIERS IN IMMUNOLOGY
(2021)
Review
Immunology
Sonia Ghilas, Ryan O'Keefe, Lisa Anna Mielke, Dinesh Raghu, Michael Buchert, Matthias Ernst
Summary: The gut epithelium serves as a physical barrier and facilitates interactions between bacteria, immune cells, and immune system components. Maintaining the integrity of the epithelial barrier is crucial for health and involves a complex response from various immune cells. Imbalance in this process can lead to chronic inflammation, tumorigenesis, and compromised immune control. In this article, the roles of innate lymphoid cells, macrophages, and dendritic cells in maintaining the epithelial barrier are discussed, highlighting their connection to both innate and adaptive immunity. These interactions impact the gut epithelium's renewal capacity, protect against tumor formation, and influence the gut microbiome, which contributes to cellular homeostasis in the gut.
FRONTIERS IN IMMUNOLOGY
(2022)
Review
Immunology
Dan Yang, Xinning Guo, Tingxuan Huang, Chuntao Liu
Summary: Innate lymphoid cells play a crucial role in maintaining mucosal homeostasis and protecting against pathogens, with ILC3s emerging as key mediators of mucosal protection and repair through producing IL-17 and IL-22. Further research is needed to understand the role of pulmonary ILC3s in respiratory infections and chronic pulmonary inflammatory diseases.
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY
(2021)
Review
Biochemistry & Molecular Biology
Ramon A. Lujan, Sophia M. Vrba, Heather D. Hickman
Summary: Before the adaptive immune response, innate antiviral cells, including conventional natural killer cells (cNK) and tissue-resident ILCs (ILC1s), respond to a wide range of viruses to limit replication and virus-induced pathology. While cNK cells lyse virus-infected cells, ILC1s respond with the production of antiviral cytokines and can even induce an antiviral state in uninfected tissue. Mounting evidence suggests that ILC1s may have enhanced secondary responses to viral infections.
JOURNAL OF MOLECULAR BIOLOGY
(2022)
Article
Immunology
Xiaopeng Wu, Achia Khatun, Moujtaba Y. Kasmani, Yao Chen, Shikan Zheng, Samantha Atkinson, Christine Nguyen, Robert Burns, Elizabeth J. Taparowsky, Nita H. Salzman, Timothy W. Hand, Weiguo Cui
Summary: This study reveals that BATF is a key factor in maintaining the stability of ILC3s in the gut and in coordinating ILC3-mediated control of intestinal homeostasis. Depletion of BATF in ILC3s leads to excessive interferon-gamma production, dysbiosis, aberrant T cell immune responses, and spontaneous inflammatory bowel disease.
JOURNAL OF EXPERIMENTAL MEDICINE
(2022)
Article
Chemistry, Multidisciplinary
Feng Li, Zhou Liang, Haojie Zhong, Xinrong Hu, Ziwen Tang, Changjian Zhu, Jiani Shen, Xu Han, Ruoni Lin, Ruilin Zheng, Ruihan Tang, Huajing Peng, Xunhua Zheng, Chengqiang Mo, Peisong Chen, Xin Wang, Qiong Wen, Jianbo Li, Xi Xia, Hongjian Ye, Yagui Qiu, Jianwen Yu, Dongying Fu, Jiaqi Liu, Rong Wang, Huixin Xie, Yun Guo, Xiaoyan Li, Jinjin Fan, Qinghua Liu, Haiping Mao, Wei Chen, Yi Zhou
Summary: In lupus nephritis (LN), gut-derived group 3 innate lymphoid cells (ILC3s) migrate from the small intestine to the kidney via the CXCR6/CXCL16 axis, contributing to the progression of LN, including spleen and lymph node enlargement, antibody production, and renal injury. In renal ectopic lymphoid structures (ELS), ILC3s induce B cell activation in a Delta-like1 (DLL1)/Notch-dependent manner, accompanied by up-regulation of Deltex1 and MAML1.
Review
Neurosciences
Nicolas Jacquelot, Gabrielle T. Belz, Cyril Seillet
Summary: The Earth's rotation creates biological clocks that regulate physiological processes and immune system. Neuroimmune interactions play a role in rhythmic activity of immune cells, and disruption of these rhythms can lead to chronic inflammation in murine models.
FRONTIERS IN NEUROSCIENCE
(2021)
Review
Biochemistry & Molecular Biology
Angela Saez, Raquel Gomez-Bris, Beatriz Herrero-Fernandez, Claudia Mingorance, Cristina Rius, Jose M. Gonzalez-Granado
Summary: Inflammatory bowel disease (IBD) is a complex condition involving chronic intestinal inflammation and is associated with genetics, environment, immune system, and intestinal barrier function. Recent studies have shown that innate lymphoid cells (ILCs) play crucial roles in intestinal homeostasis and IBD.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Gastroenterology & Hepatology
Chupeng Hu, Bingqing Xu, Xiaodong Wang, Wen-Hua Wan, Jinying Lu, Deyuan Kong, Yu Jin, Wenhua You, Hua Sun, Xiaoxin Mu, Dongju Feng, Yun Chen
Summary: This study found that reduced levels of Lactobacillus reuteri and short-chain fatty acids (SCFAs) were associated with hepatocellular carcinoma (HCC) development. Acetate reduced IL-17A production in hepatic ILC3s by inhibiting histone deacetylase activity. Tumor-infiltrating ILC3s correlated with prognosis in HCC patients, which may be mediated by acetate. Modifying bacteria, changing SCFAs, reducing IL-17A-producing ILC3 infiltration, and combining with immune checkpoint inhibitors may contribute to the clinical treatment of HCC.
Article
Immunology
Zhengzheng Shi, Tadashi Takeuchi, Yumiko Nakanishi, Tamotsu Kato, Katharina Beck, Ritsu Nagata, Tomoko Kageyama, Ayumi Ito, Hiroshi Ohno, Naoko Satoh-Takayama
Summary: Daikenchuto (DKT) is a widely used Japanese herbal formula for gastrointestinal disorders. This study found that DKT has anti-inflammatory effects in a mouse model of colitis, reducing the severity of colitis and maintaining symbiotic microbiota. DKT also protected colonic epithelial integrity and restored reduced innate lymphoid cells (ILC3s) levels. This research provides insights into the molecular basis of herbal medicine and contributes to future drug development.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Gastroenterology & Hepatology
Na Li, Peiguang Ma, Yalan Li, Xuekai Shang, Xinmei Nan, Lei Shi, Xiao Han, Jiajing Liu, Yanfei Hong, Qiuyi Li, Jiaqi Cui, Junxiang Li, Guiying Peng
Summary: Intestinal microbiota dysbiosis and metabolic disruption are well-known triggers of ulcerative colitis. However, their role in regulating ILC3s, which are crucial for intestinal health, has not been explored. This study found that the microbiota structure of severe UC patients differed from those with mild UC, moderate UC, and healthy controls. Microbes producing secondary bile acids decreased with the worsening of UC, and there was a strong positive correlation between them. The study also showed that microbiota-mediated inflammatory modulation increased with disease severity, leading to reduced ILC3 percentage and down-regulated bile acid receptor expressions.
Article
Gastroenterology & Hepatology
Xingyuan Xu, Longyun Ye, Qi Zhang, Hang Shen, Shanshan Li, Xiaoyu Zhang, Mao Ye, Tingbo Liang
Summary: The study revealed that ILC2s were highly enriched in human HCC and significantly correlated with tumor recurrence, progression-free survival, and overall survival in patients. The HCC-associated ILC2s were identified as an immune regulatory cell type that promotes tumor development, suggesting potential new treatments for HCC by targeting these cells.
Article
Biochemistry & Molecular Biology
Ying Kong, Han-Dong Li, Dan Wang, Xiaolin Gao, Chunsheng Yang, Minshu Li, Ting Chang, Qiang Liu
Summary: The study found a correlation between the reduction of ILC2 and disease severity in neuromyelitis optica spectrum disorder (NMOSD), and expanding ILC2 could alleviate the pathological conditions.
Review
Immunology
Takahiro Matsuyama, Hiromi Matsuyama, Yoichi Dotake, Koichi Takagi, Kentaro Machida, Hiromasa Inoue
Summary: T helper type 2 cells and group 2 innate lymphoid cells play a crucial role in asthma, particularly in airway eosinophilic inflammation. These cells are activated by cytokines released by airway epithelial cells and produce high levels of type 2 cytokines. ILC2s induce airway inflammation independently of antigens and may contribute to steroid resistance. Biologics targeting these cytokines and/or their receptors have shown promise in reducing asthma exacerbations and improving lung function and quality of life in asthmatic patients.
FRONTIERS IN IMMUNOLOGY
(2022)
Review
Biochemistry & Molecular Biology
Ziyu Wang, Jun Wang
Summary: ILCs, as innate immune cells, play a crucial role in maintaining homeostasis and are associated with a variety of gastrointestinal diseases due to their complex and pleiotropic characteristics. Their ability to transition among subgroups allows them to function both as promoting and inhibiting cells, impacting disease progression towards either alleviation or deterioration.
JOURNAL OF GENETICS AND GENOMICS
(2021)
Article
Dermatology
Suiting Ao, Xuemei Gao, Jipang Zhan, Lu Ai, Minyi Li, Huilin Su, Xuhua Tang, Coco Chu, Jiande Han, Fang Wang
Summary: The combination of TNF-alpha inhibition and steroids showed better outcomes in treating SJS/TEN compared to steroid monotherapy, significantly shortening the duration of acute phase, hospitalization stay, and skin reepithelialization time. IL-15 was positively correlated with skin reepithelialization time in both groups, while IL-6 served as an additional marker for disease progression in the combination therapy group.
JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY
(2022)
Article
Immunology
Lei Zhou, Wenqing Zhou, Ann M. Joseph, Coco Chu, Gregory G. Putzel, Beibei Fang, Fei Teng, Mengze Lyu, Hiroshi Yano, Katrin I. Andreasson, Eisuke Mekada, Gerard Eberl, Gregory F. Sonnenberg
Summary: Group 3 innate lymphoid cells (ILC3s) protect the intestine from TNF-induced cell death by producing heparin-binding epidermal growth factor-like growth factor (HB-EGF), thereby playing a crucial role in inflammatory bowel disease (IBD).
Article
Oncology
Manish A. Shah, Kohei Shitara, Florian Lordick, Yung-Jue Bang, Niall C. Tebbutt, Jean-Phillippe Metges, Kei Muro, Keun-Wook Lee, Lin Shen, Sergei Tjulandin, John L. Hays, Naureen Starling, Rui-Hua Xu, Keren Sturtz, Marilyn Fontaine, Cindy Oh, Emily M. Brooks, Bo Xu, Wei Li, Chiang J. Li, Laura Borodyansky, Eric Van Cutsem
Summary: Adding napabucasin to paclitaxel did not improve survival in patients with second-line advanced gastric or gastroesophageal junction adenocarcinoma. The safety profile of napabucasin was driven by manageable gastrointestinal events, with grade >= 3 diarrhea occurring at a higher frequency with napabucasin plus paclitaxel versus placebo plus paclitaxel.
CLINICAL CANCER RESEARCH
(2022)
Article
Oncology
Manish A. Shah, Anghel Adrian Udrea, Igor Bondarenko, Was Mansoor, Raquel Guardeno Sanchez, Tomasz Sarosiek, Silvia Bozzarelli, Michael Schenker, Carlos Gomez-Martin, Carys Morgan, Mustafa oezgueroglu, Joanna Pikiel, Haralabos P. Kalofonos, Elzbieta Wojcik, Tomas Buchler, Daniel Swinson, Irfan Cicin, Mano Joseph, Ihor Vynnychenko, Alexander Valerievich Luft, Peter C. Enzinger, Tomas Salek, Christos Papandreou, Christophe Tournigand, Evaristo Maiello, Ran Wei, David Ferry, Ling Gao, Joana M. Oliveira, Jaffer A. Ajani
Summary: Ramucirumab at a dosage of 8 mg/kg every 2 weeks is a standard treatment option for second-line advanced/metastatic gastric/gastroesophageal junction adenocarcinoma, either as monotherapy or in combination with paclitaxel. Different dosing regimens were explored in these studies, but there was no dose/exposure-response relationship supporting the use of the standard dose of ramucirumab.
Article
Multidisciplinary Sciences
Wenqing Zhou, Lei Zhou, Jordan Zhou, Coco Chu, Chao Zhang, Robbyn E. Sockolow, Gerard Eberl, Gregory F. Sonnenberg
Summary: This study defines ROR gamma t(+) immune cells in the intestine at single-cell resolution and identifies a subset of ILC3s that expresses ZBTB46, a transcription factor shared with conventional dendritic cells. ZBTB46 restrains the inflammatory properties of ILC3s and plays a non-redundant role in orchestrating intestinal health.
Article
Oncology
Josep Tabernero, Paulo M. Hoff, Lin Shen, Atsushi Ohtsu, Manish A. Shah, Asna Siddiqui, Sarah Heeson, Astrid Kiermaier, Harrison Macharia, Eleonora Restuccia, Yoon-Koo Kang
Summary: This study aimed to evaluate the long-term efficacy and safety of pertuzumab plus trastuzumab and chemotherapy in previously untreated HER2-positive metastatic gastric or gastroesophageal junction cancer. The results showed increased overall survival and progression-free survival, higher objective response rate, and comparable safety in the pertuzumab arm.
Article
Oncology
Manish A. Shah, Takayuki Yoshino, Niall C. Tebbutt, Axel Grothey, Josep Tabernero, Rui-Hua Xu, Andres Cervantes, Sang Cheul Oh, Kensei Yamaguchi, Marwan Fakih, Alfredo Falcone, Christina Wu, Vi K. Chiu, Jiri Tomasek, Johanna Bendell, Marilyn Fontaine, Matthew Hitron, Bo Xu, Julien Taieb, Eric Van Cutsem
Summary: In this study, patients with colorectal cancer were divided into two groups, one receiving combination therapy of napabucasin and FOLFIRI, and the other receiving FOLFIRI alone. The results showed that the addition of napabucasin to FOLFIRI did not significantly improve overall survival compared to the control group.
CLINICAL COLORECTAL CANCER
(2023)
Article
Oncology
Manish A. Shah, Erin B. Kennedy, Ashley E. Alarcon-Rozas, Thierry Alcindor, Angela N. Bartley, Aubrey Belk Malowany, Nishin A. Bhadkamkar, Dana C. Deighton, Yelena Janjigian, Asha Karippot, Uqba Khan, Daniel A. King, Kelsey Klute, Jill Lacy, James J. Lee, Rutika Mehta, Sarbajit Mukherjee, Arun Nagarajan, Haeseong Park, Anwaar Saeed, Thomas J. Semrad, Kohei Shitara, Elizabeth Smyth, Nataliya Uboha, Melani Vincelli, Zev Wainberg, Lakshmi Rajdev
Summary: The purpose of this study is to develop recommendations for targeted therapies in advanced gastroesophageal cancer. A systematic review was conducted, and 18 randomized controlled trials were included. The recommendations include first-line therapy with nivolumab and chemotherapy for HER2-negative patients with gastric adenocarcinoma and PD-L1 CPS >= 5, and pembrolizumab and chemotherapy for HER2-negative patients with esophageal or gastroesophageal junction AC and PD-L1 CPS >= 10. Clinical trials are recommended as targeted treatment options for gastroesophageal cancer are expected to evolve.
JOURNAL OF CLINICAL ONCOLOGY
(2023)
Article
Multidisciplinary Sciences
Walid K. Chatila, Henry Walch, Jaclyn F. Hechtman, Sydney M. Moyer, Valeria Sgambati, David M. Faleck, Amitabh Srivastava, Laura Tang, Jamal Benhamida, Dorina Ismailgeci, Carl Campos, Fan Wu, Qing Chang, Efsevia Vakiani, Elisa de Stanchina, Martin R. Weiser, Maria Widmar, Rhonda K. Yantiss, Manish A. Shah, Adam J. Bass, Zsofia K. Stadler, Lior H. Katz, Ingo K. Mellinghoff, Nilay S. Sethi, Nikolaus Schultz, Karuna Ganesh, David Kelsen, Rona Yaeger
Summary: Inflammation is recognized as a contributing factor to cancer development, particularly in the gastrointestinal tract. In this study, the clinical features, genomic landscape, and germline alterations of colitis-associated cancers were defined. TP53 alterations were a common event in colitis-associated cancers, occurring in half of dysplasia, while Wnt pathway alterations were infrequent. The sequencing results from multiple dysplasia/cancer lesions suggest that these lesions largely occur as genetically independent events with lineage plasticity away from Wnt activation.
NATURE COMMUNICATIONS
(2023)
Article
Oncology
Olivia Fankuchen, Jennifer Lau, Mangala Rajan, Brandon Swed, Peter Martin, Manuel Hidalgo, Samuel Yamshon, Laura Pinheiro, Manish A. Shah
Summary: This study examined the long-term effects of COVID-19 infection in cancer patients and found that cancer patients had higher mortality rates after hospital discharge. Additionally, approximately one-third of all patients experienced long COVID symptoms.
AMERICAN JOURNAL OF CLINICAL ONCOLOGY-CANCER CLINICAL TRIALS
(2023)
Article
Medicine, General & Internal
Kohei Shitara, Florian Lordick, Yung-Jue Bang, Peter Enzinger, David Ilson, Manish A. Shah, Eric Van Cutsem, Rui-Hua Xu, Giuseppe Aprile, Jianming Xu, Joseph Chao, Roberto Pazo-Cid, Yoon-Koo Kang, Jianning Yang, Diarmuid Moran, Pranob Bhattacharya, Ahsan Arozullah, Jung Wook Park, Mok Oh, Jaffer A. Ajani
Summary: Zolbetuximab in combination with mFOLFOX6 significantly prolongs progression-free survival and overall survival in patients with CLDN18.2-positive, HER2-negative, locally advanced unresectable or metastatic gastric or gastro-oesophageal junction adenocarcinoma, with good safety profile.
Review
Oncology
Manish A. Shah, Nasser Altorki, Pretish Patel, Sebron Harrison, Adam Bass, Julian A. Abrams
Summary: Oesophageal cancer is a common malignancy with significant morbidity and mortality. Advances in disease understanding, screening, monitoring technologies, surgical techniques, radiotherapy, and systemic therapy have improved patient outcomes. The development of minimally invasive diagnostic technologies based on cancer-specific genomic or epigenetic alterations has the potential to enhance screening. Less invasive surgical techniques and immune-checkpoint inhibitors also hold promise in improving treatment. This review discusses these advances and highlights the ongoing transformation in oesophageal cancer management.
NATURE REVIEWS CLINICAL ONCOLOGY
(2023)
Editorial Material
Oncology
Lakshmi Rajdev, Erin B. Kennedy, Manish A. Shah
JCO ONCOLOGY PRACTICE
(2023)
Article
Biochemistry & Molecular Biology
Manish A. Shah, Kohei Shitara, Jaffer A. Ajani, Yung-Jue Bang, Peter Enzinger, David Ilson, Florian Lordick, Eric Van Cutsem, Javier Gallego Plazas, Jing Huang, Lin Shen, Sang Cheul Oh, Patrapim Sunpaweravong, Hwoei Fen Soo Hoo, Haci Mehmet Turk, Mok Oh, Jung Wook Park, Diarmuid Moran, Pranob Bhattacharya, Ahsan Arozullah, Rui-Hua Xu
Summary: The GLOW trial demonstrated that zolbetuximab, a monoclonal antibody targeting CLDN18.2, combined with CAPOX, significantly improved progression-free survival and overall survival in patients with CLDN18.2-positive, HER2-negative, locally advanced unresectable or metastatic gastric or gastroesophageal junction adenocarcinoma.
Article
Oncology
Jung Eun Baik, Li Li, Manish A. Shah, Daniel E. Freedberg, Zhezhen Jin, Timothy C. Wang, Yiping W. Han
Summary: Fusobacterium nucleatum (Fn) is a common gram-negative anaerobic bacterium that promotes colorectal cancer development through the secretion of FadAc. This study found that circulating levels of anti-FadAc IgA were significantly increased in patients with colorectal cancer, particularly in those with proximal tumors. Therefore, anti-FadAc IgA may serve as a serological biomarker for early detection of colorectal cancer.
CANCER RESEARCH COMMUNICATIONS
(2022)