Review
Biochemistry & Molecular Biology
Soon Kyu Lee, Jong Young Choi, Eun Sun Jung, Jung Hyun Kwon, Jeong Won Jang, Si Hyun Bae, Seung Kew Yoon
Summary: The liver is constantly exposed to potentially toxic substances and plays a crucial role in clearing foreign agents through innate and adaptive immune cells. Drug induced liver injury (DILI) caused by medications, herbs, and dietary supplements has become a significant concern in liver diseases. Reactive metabolites or drug-protein complexes activate innate and adaptive immune cells, resulting in DILI. The review focuses on the immunological mechanism of DILI, provides drug treatment targets, describes the mechanisms of DILI, and details the management of DILI caused by drugs for hepatocellular carcinoma (HCC) and liver transplantation (LT).
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Biochemistry & Molecular Biology
Justyna Blach, Kamila Wojas-Krawczyk, Marcin Nicos, Pawel Krawczyk
Summary: Immune checkpoint inhibitors have a significant impact on clinical treatment outcomes in NSCLC, but many patients develop resistance to this therapy. Currently, there is a lack of reliable biomarkers for predicting sensitivity to immune therapy. Research is focused on using immunotherapy in combination with other treatment strategies to increase cancer immunogenicity by targeting immune checkpoints and the tumor microenvironment.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Immunology
Yoshiko Takeuchi, Tokiyoshi Tanegashima, Eiichi Sato, Takuma Irie, Atsuo Sai, Kota Itahashi, Shogo Kumagai, Yasuko Tada, Yosuke Togashi, Shohei Koyama, Esra A. Akbay, Takahiro Karasaki, Keisuke Kataoka, Soichiro Funaki, Yasushi Shintani, Izumi Nagatomo, Hiroshi Kida, Genichiro Ishii, Tomohiro Miyoshi, Keiju Aokage, Kazuhiro Kakimi, Seishi Ogawa, Meinoshin Okumura, Masatoshi Eto, Atsushi Kumanogoh, Masahiro Tsuboi, Hiroyoshi Nishikawa
Summary: Highly mutated NSCLC with activation of the WNT/β-catenin pathway leads to impaired immune cell infiltration into the tumor microenvironment, resulting in resistance to PD-1 blockade therapy. Combination therapy with PD-1 blockade and WNT/β-catenin signaling inhibitors shows enhanced antitumor immunity compared to monotherapy.
SCIENCE IMMUNOLOGY
(2021)
Article
Oncology
Faisal Fa'ak, Maryam Buni, Adewunmi Falohun, Huifang Lu, Juhee Song, Daniel H. Johnson, Chrystia M. Zobniw, Van A. Trinh, Muhammad Osama Awiwi, Nourel Hoda Tahon, Khaled M. Elsayes, Kaysia Ludford, Emma J. Montazari, Julia Chernis, Maya Dimitrova, Sabina Sandigursky, Jeffrey A. Sparks, Osama Abu-Shawer, Osama Rahma, Uma Thanarajasingam, Ashley M. Zeman, Rafee Talukder, Namrata Singh, Sarah H. Chung, Petros Grivas, May Daher, Ala Abudayyeh, Iman Osman, Jeffrey Weber, Jean H. Tayar, Maria E. Suarez-Almazor, Noha Abdel-Wahab, Adi Diab
Summary: This retrospective study evaluated the safety and effectiveness of anti-interleukin-6 receptor (anti-IL-6R) therapy for immune-related adverse events (irAEs). The results showed that anti-IL-6R treatment can improve irAEs without hindering antitumor immunity.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2023)
Article
Oncology
Rom Leidner, Kevin Conlon, Douglas G. Mcneel, Andrea Wang-Gillam, Sumati Gupta, Robert Wesolowski, Monica Chaudhari, Nadia Hassounah, Jong Bong Lee, Lang Ho Lee, Jessica A. O'Keeffe, Nancy Lewis, George N. Pavlakis, John A. Thompson
Summary: This study investigated the efficacy and safety of NIZ985 as monotherapy and in combination with spartalizumab in the treatment of advanced solid tumors. The results showed that NIZ985 demonstrated antitumor activity and was well tolerated in patients with advanced solid tumors.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2023)
Article
Oncology
Nicola Personeni, Tiziana Pressiani, Antonio D'Alessio, Maria Giuseppina Prete, Silvia Bozzarelli, Luigi Terracciano, Arianna Dal Buono, Antonio Capogreco, Alessio Aghemo, Ana Lleo, Romano Fabio Lutman, Massimo Roncalli, Laura Giordano, Armando Santoro, Luca Di Tommaso, Lorenza Rimassa
Summary: Hepatitis is a common immune-related adverse event in patients with hepatocellular carcinoma receiving immunotherapy, with risk factors including high baseline ALT levels and infectious HCC etiology. However, high-grade hepatitis has a benign course, allowing safe resumption of treatment without affecting treatment outcomes. Further investigation on biological features reminiscent of the HCC immune class is warranted to better understand and prevent high-grade hepatitis development in these patients.
Article
Biochemistry & Molecular Biology
Yukinori Endo, Katie L. Winarski, Md Sanaullah Sajib, Anna Ju, Wen Jin Wu
Summary: Atezolizumab, an immune checkpoint inhibitor targeting PD-L1, may cause liver toxicity by inducing PD-L1-mediated cell death in hepatocytes.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Gastroenterology & Hepatology
Nelia Hernandez, Fernando Bessone
Summary: Novel biological agents are being used to treat various diseases and are being evaluated in hepatocellular carcinoma. Some of these agents can cause liver damage, and liver biopsy is useful for diagnosis.
JOURNAL OF CLINICAL AND TRANSLATIONAL HEPATOLOGY
(2022)
Review
Immunology
Xuewei Li, Lina Ji, Xiaofang Li, Dong Sun, Wenhui Yang
Summary: The use of immune checkpoint inhibitors (ICIs) can improve survival of patients with malignant tumors, but is also associated with unpredictable immune-related adverse effects (irAEs). This study reports two cases of severe immune-mediated hepatotoxicity (IMH) in patients with metastatic malignant gastrointestinal tumors after ICI therapy. Both cases were successfully treated with immunosuppressive therapy and non-biological artificial liver, resulting in restored liver function and maintained anti-tumor treatment effect.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Gastroenterology & Hepatology
Edmond Atallah, Sarah J. Welsh, Brent O'Carrigan, Ana Oshaughnessy, Igboin Dolapo, Andrew S. Kerr, Joanna Kucharczak, Colin Y. C. Lee, Colin Crooks, Amy Hicks, Chenchu Ramu Chimakurthi, Ankit Rao, Hester Franks, Poulam M. Patel, Guruprasad P. Aithal
Summary: The real-world risk of checkpoint inhibitor-induced liver injury (ChILI) is higher than previously reported, and combination therapy, female sex, higher baseline alanine transferase level, and lower baseline alkaline phosphatase level are independent risk factors. The Common Terminology Criteria for Adverse Events overestimates the clinical severity of ChILI, calling for revision in case definition, evaluation, and management to harmonize care.
Article
Pediatrics
Yu-ming Guo, Fei-lin Ge, Hai-bo Song, Peng Xiong, Jing Jing, Ming Niu, Xu Zhao, Zhao-fang Bai, Jia-bo Wang, Xiao-he Xiao
Summary: Children, especially infants, are sensitive to liver-related adverse drug reactions caused by several specific drug categories.
JOURNAL OF PEDIATRICS
(2021)
Review
Pharmacology & Pharmacy
Tao Wang, Matthew M. Yeh, Mark I. Avigan, Lorraine Pelosof, Gerald M. Feldman
Summary: The liver microenvironment plays a crucial role in the occurrence and treatment of ILICI. Understanding and identifying the roles of liver cells in regulating immune homeostasis and hepatocyte regeneration are crucial for the prognosis and treatment of ILICI.
Article
Biochemistry & Molecular Biology
Jae Ho Choi, Sun Woo Jin, Gi Ho Lee, Eun Hee Han, Yong Pil Hwang, Hye Gwang Jeong
Summary: Rutaecarpine shows protective effects against acetaminophen-induced liver toxicity by reducing liver damage indicators, inhibiting inflammatory cytokine expression, and enhancing antioxidant enzyme activity, indicating its great therapeutic potential in treating liver injury.
Review
Immunology
Rebecca Adams, Jack E. M. Coumbe, Ben G. T. Coumbe, Jennifer Thomas, Zena Willsmore, Marija Dimitrievska, Monica Yasuzawa-Parker, Maximilian Hoyle, Suhaylah Ingar, Jenny L. C. Geh, Alastair D. MacKenzie Ross, Ciaran Healy, Sophie Papa, Katie E. Lacy, Sophia N. Karagiannis
Summary: This review discusses the effects of MAPKi, especially BRAFi, on the tumor microenvironment, focusing on changes in inflammatory cytokine secretion, immune cell recruitment, and functions during response to BRAFi treatment and development of resistance. The authors outline potential combinations of MAPKi with established and experimental therapies. Using MAPKi in combination with established treatments may enhance immunological effects and reverse immune suppression in melanoma treatment.
EXPERT REVIEW OF CLINICAL IMMUNOLOGY
(2022)
Article
Oncology
Linnea A. Swanson, Ihab Kassab, Irene Tsung, Bryan J. Schneider, Robert J. Fontana
Summary: This study aimed to investigate the incidence, etiology, and outcomes of liver injury in patients receiving durvalumab-based immunotherapy. The results showed that liver injury was associated with a higher likelihood of tumor progression and death. The development of liver injury during treatment and baseline hepatic metastases were independently associated with mortality. This highlights the importance of causality assessment in determining the cause of liver injury in cancer patients receiving immunotherapy.
FRONTIERS IN ONCOLOGY
(2022)