Review
Oncology
Alessandra Ruenger, Dirk Schadendorf, Axel Hauschild, Christoffer Gebhardt
Summary: Clinical trials studying immune checkpoint inhibitors (ICIs) have excluded immunocompromised patients. This study reviewed the existing literature and analyzed treatment outcomes of 144 patients. The findings suggest that effective immunotherapy with retained transplant was achieved in approximately 30.8% of patients. The overall response rates of immunotherapy were similar to non-immunocompromised cancer patients, but publication bias may overestimate positive outcomes.
EUROPEAN JOURNAL OF CANCER
(2022)
Article
Surgery
Lissa Pipeleers, Daniel Abramowicz, Nilufer Broeders, Alain Lemoine, Patrick Peeters, Steven Van Laecke, Laurent E. Weekers, Jacques Sennesael, Karl M. Wissing, Caroline Geers, Jean-Louis Bosmans
Summary: Withdrawal of steroids or switching to everolimus instead of cyclosporine are two effective strategies to reduce treatment-related side effects and improve long-term outcomes of kidney transplantation. Both regimens provide similar 5-year patient survival and death-censored graft survival, but the everolimus group showed higher (51)CrEDTA clearance at 1 and 5 years post-transplantation.
TRANSPLANT INTERNATIONAL
(2021)
Article
Immunology
S. Bos, L. J. De Sadeleer, J. Yserbyt, L. J. Dupont, L. Godinas, G. M. Verleden, L. J. Ceulemans, B. M. Vanaudenaerde, R. Vos
Summary: Among the lung transplant recipients included in this study, 13% received mTORi treatment, mostly due to renal insufficiency and malignancy. However, half of the patients discontinued mTORi therapy after experiencing adverse events or drug toxicity.
INTERNATIONAL IMMUNOPHARMACOLOGY
(2021)
Article
Chemistry, Multidisciplinary
Hong Sik Shin, Sohyun Kim, Seung Mo Jin, Yeon Jeong Yoo, Jang Hun Heo, Yong Taik Lim
Summary: This study proposes a dynamic immunomodulation strategy that addresses the limitations of systemic immune toxicity and tolerance in TLR7/8a therapy. It involves the use of prodrug-like TLR7/8a to control its activity and nanoliposomes for sustained release. The strategy activates innate immune cells and antigen-specific T cell responses, reprogramming immunosuppressive cells and reducing adverse effects. The results suggest the potential of this strategy for safe and effective cancer immunotherapy.
ADVANCED MATERIALS
(2023)
Article
Immunology
Elena Crespo, Anna Vidal-Alabro, Thomas Jouve, Pere Fontova, Maik Stein, Sonila Mocka, Maria Meneghini, Anett Sefrin, Petra Hruba, Montserrat Goma, Alba Torija, Laura Donadeu, Alex Fava, Josep M. Cruzado, Edoardo Melilli, Francesc Moreso, Ondrej Viklicky, Frederike Bemelman, Petra Reinke, Josep Grinyo, Nuria Lloberas, Oriol Bestard
Summary: This study investigated how functional TAC-CYP3A genetic variants influence the risk of biopsy-proven acute rejection (BPAR) in kidney transplant patients. The results showed that different genetic variants impacted TAC exposure levels and predicted the occurrence of BPAR. Combining genetic variants with other clinical and immunological risk factors may improve the prediction of rejection risk.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Gastroenterology & Hepatology
Clement Barjon, Geraldine Dahlqvist, Khaldoun Ghazal, Faouzi Saliba, Francois Durand, Christophe Duvoux, Lynda Aoudjehane, Filomena Conti
Summary: This study monitored Tregs levels and functionality in liver transplant patients under different immunosuppressive drugs, finding that everolimus may have a more positive impact on Tregs compared to tacrolimus. This provides a new approach for reducing the use of immunosuppressive drugs.
CLINICS AND RESEARCH IN HEPATOLOGY AND GASTROENTEROLOGY
(2021)
Review
Immunology
Michelle F. Huffaker, Srinath Sanda, Sindhu Chandran, Sharon A. Chung, E. William St Clair, Gerald T. Nepom, Dawn E. Smilek
Summary: The article reviews concepts evolved from the clinical trial experience of the Immune Tolerance Network, focusing on lessons learned from innovative mechanistic studies and new strategies for tolerance induction.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Urology & Nephrology
David Wojciechowski, Alexander Wiseman
Summary: The long-term management of maintenance immunosuppression in kidney transplant recipients is complex, with various drug regimens having their own advantages and disadvantages. Balancing between treatment efficacy and adverse effects is crucial in decision-making for these patients.
CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
(2021)
Article
Immunology
Vera Petrova, Christopher Groth, Rebekka Bitsch, Ihor Arkhypov, Sonja C. S. Simon, Svetlana Hetjens, Verena Mueller, Jochen Utikal, Viktor Umansky
Summary: This study investigated the dynamic changes in immunosuppressive pattern and activity of myeloid-derived suppressor cells (MDSC) in melanoma patients treated with immune checkpoint inhibitors (ICI). It was found that non-responders had higher frequency and immunosuppressive activity of MDSC compared to responders. Additionally, non-responders had higher concentrations of IL-6 and IL-8 before therapy and after the first ICI application compared to responders.
FRONTIERS IN IMMUNOLOGY
(2023)
Review
Oncology
Letizia Todeschini, Luca Cristin, Alessandro Martinino, Amelia Mattia, Salvatore Agnes, Francesco Giovinazzo
Summary: Liver transplantation is an effective treatment option for nonresectable patients with early-stage HCC, especially when they meet the Milan criteria. However, the use of CNIs for immunosuppression increases the risk of tumor regrowth. mTOR inhibitors have emerged as an alternative immunosuppressive approach that can address both immunosuppression and cancer control. This review summarizes the roles of mTOR inhibitors in managing HCC patients undergoing LT and proposes strategies to overcome common adverse effects.
Article
Immunology
Qian Xing, Zhongwei Zhang, Biao Zhu, Qionghua Lin, Lihua Shen, Fangfang Li, Zhili Xia, Zhiyong Zhao
Summary: This article reports a case of immune-related myocarditis in a patient with stage IV nasopharyngeal carcinoma during immune checkpoint inhibitor therapy. Tofacitinib, targeting the Janus kinase-signal transducer and activator of transcription signal pathway, was successfully used in the treatment of steroid-refractory immune-related myocarditis. The patient showed improvement without major adverse cardiac events.
FRONTIERS IN IMMUNOLOGY
(2022)
Review
Medical Laboratory Technology
Florian Lemaitre, Klemens Budde, Teun Van Gelder, Stein Bergan, Roland Lawson, Ofelia Noceti, Raman Venkataramanan, Laure Elens, Dirk Jan A. R. Moes, Dennis A. Hesselink, Tomasz Pawinski, Kamisha L. Johnson-Davis, Brenda C. M. De Winter, Smita Pattanaik, Merce Brunet, Satohiro Masuda, Loralie J. Langman
Summary: Nirmatrelvir/ritonavir (Paxlovid) is a combination of a peptidomimetic inhibitor (nirmatrelvir) and a pharmacokinetic enhancer (ritonavir) that is approved for the treatment of mild-to-moderate COVID-19. The ritonavir component of this combination can cause significant drug-drug interactions (DDIs) by inhibiting the metabolism of nirmatrelvir. This may lead to higher plasma concentrations of nirmatrelvir and a longer half-life. Co-administration of nirmatrelvir/ritonavir with immunosuppressive drugs (ISDs) is particularly challenging due to the involvement of the same metabolic pathway and the increased risk of adverse drug reactions.
THERAPEUTIC DRUG MONITORING
(2023)
Article
Urology & Nephrology
Emel Isiktas Sayilar, Alparslan Ersoy, Canan Ersoy, Aysegul Oruc, Yavuz Ayar, Deniz Sigirli
Summary: This study investigated the effect of calcineurin inhibitors on anthropometrics in kidney transplant recipients. The results showed that after kidney transplantation, most recipients experienced increases in body weight and body mass index. The type of calcineurin inhibitor did not significantly affect weight gain. However, caution should be exercised regarding the dyslipidemic effect of cyclosporine and the potential hazards of using tacrolimus in patients with a diabetic predisposition.
Article
Immunology
Jihoon G. Yoon, Seung Hwan Song, Sungkyoung Choi, Jaeseong Oh, In-Jin Jang, Young Jin Kim, Sanghoon Moon, Bong-Jo Kim, Yuri Cho, Hyo Kee Kim, Sangil Min, Jongwon Ha, Ho Sik Shin, Chul Woo Yang, Hye Eun Yoon, Jaeseok Yang, Min Goo Lee, Jae Berm Park, Myoung Soo Kim
Summary: Rare variant profiling of CYP3A5 and CYP3A4, combined with haplotype structures of the CYP3A locus, provides additional value for personalized TAC dosing. Moreover, a novel association between rare variants of CYP1A1 and TAC PK variability in CYP3A5 nonexpressers was identified, warranting further investigation.
Review
Biochemistry & Molecular Biology
Amanda Reyes, Atish Mohanty, Rebecca Pharaon, Erminia Massarelli
Summary: This review examines the complex interactions between immune system activation and deactivation and the development of malignant tumors, as well as the link between autoimmunity and cancer rates. Furthermore, it focuses on the main classes of immune inhibitor therapy used in transplant patients and in autoimmune diseases, such as TNF-alpha, Calcineurin, mTOR, purine synthesis antagonists, and IMPDH inhibitors.
Article
Surgery
Elliot Merritt, Maria-Carlota Londono, Kate Childs, Gavin Whitehouse, Elisavet Kodela, Alberto Sanchez-Fueyo, Marc Martinez-Llordella
Summary: HCV infection leads to generation of HCV-specific CD8(+) T cells capable of reacting against allogeneic HLA molecules, and LT recipients with HCV positivity show higher expression of inhibitory receptors (PD-1/CTLA4). Viral clearance significantly reverses decreased responses to donor and third-party antigens, and increases the proportion of HCV-specific CD8(+) T cells reacting against the donor before clearance of the virus.
AMERICAN JOURNAL OF TRANSPLANTATION
(2021)
Article
Gastroenterology & Hepatology
Guru Trikudanathan, B. Joseph Elmunzer, Yi Yang, Maisam Abu-El-Haija, David Adams, Syed Ahmad, Appakalai N. Balamurugan, Gregory J. Beilman, Srinath Chinnakotla, Darwin L. Conwell, Martin L. Freeman, Timothy B. Gardner, Betul Hatipoglu, James S. Hodges, Varvara Kirchner, Luis F. Lara, Leslie Long-Simpson, Rebecca Mitchell, Katherine Morgan, Jaimie D. Nathan, Bashoo Naziruddin, Andrew Posselt, Timothy L. Pruett, Sarah J. Schwarzenberg, Vikesh K. Singh, Kerrington Smith, Martin Wijkstrom, Piotr Witkowski, Melena D. Bellin
Summary: The study found associations between pre-operative ERCP and ERCP frequency with clinical characteristics and islet yield in patients undergoing TPIAT. However, pre-operative ERCP did not significantly impact islet yield. Therefore, ERCP can be performed as needed without withholding to optimize surgical outcomes.
Article
Biotechnology & Applied Microbiology
Markus Muttenthaler, Glenn E. King, David J. Adams, Paul E. Alewood
Summary: This Perspective summarizes key trends in peptide drug discovery and development, including human hormones, elegant medicinal chemistry and rational design strategies, peptide drugs derived from nature, and major breakthroughs in molecular biology and peptide chemistry. It also emphasizes lessons from earlier approaches that are still relevant today and discusses emerging strategies impact on peptide drug discovery.
NATURE REVIEWS DRUG DISCOVERY
(2021)
Article
Pharmacology & Pharmacy
Jeffrey R. McArthur, Nehan R. Munasinghe, Rocio K. Finol-Urdaneta, David J. Adams, Macdonald J. Christie
Summary: Research has shown that Pn3a produces analgesic effects by inhibiting HVA Ca(v), with enhanced inhibition observed when co-administered with opioid agonists.
FRONTIERS IN PHARMACOLOGY
(2021)
Article
Gastroenterology & Hepatology
Richard Taubert, Bastian Engel, Jana Diestelhorst, Katharina L. Hupa-Breier, Patrick Behrendt, Niklas T. Baerlecken, Kurt-Wolfram Suehs, Maciej K. Janik, Kalliopi Zachou, Marcial Sebode, Christoph Schramm, Maria-Carlota Londono, Sarah Habes, Ye H. Oo, Claudine Lalanne, Simon Pape, Maren Schubert, Michael Hust, Stefan Duebel, Mario Thevis, Danny Jonigk, Julia Beimdiek, Falk F. R. Buettner, Joost P. H. Drenth, Luigi Muratori, David H. Adams, Jessica K. Dyson, Amedee Renand, Isabel Graupera, Ansgar W. Lohse, George N. Dalekos, Piotr Milkiewicz, Martin Stangel, Benjamin Maasoumy, Torsten Witte, Heiner Wedemeyer, Michael P. Manns, Elmar Jaeckel
Summary: This study identified more accurate autoantibodies for diagnosing autoimmune hepatitis (AIH) using a protein macroarray, which showed higher specificity and sensitivity compared to conventional autoantibodies. These antibodies could be used as promising markers to improve the diagnostic workup of liver diseases, particularly in cases of seronegative AIH.
Editorial Material
Gastroenterology & Hepatology
Julien Vionnet, Alberto Sanchez-Fueyo
LIVER TRANSPLANTATION
(2022)
Article
Gastroenterology & Hepatology
Victoria T. Kronsten, Charlotte A. Woodhouse, Ane Zamalloa, Tiong Yeng Lim, Lindsey A. Edwards, Marc Martinez-Llordella, Alberto Sanchez-Fueyo, Debbie L. Shawcross
Summary: This study investigated the immune system function in cirrhotic patients and found that they exhibit an exaggerated immune response to bacterial products, especially in decompensated patients. The intensity of the immune response may be related to the severity of liver disease.
AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY
(2022)
Article
Surgery
Katelynn S. Madill-Thomsen, Marwan Abouljoud, Chandra Bhati, Michal Ciszek, Magdalena Durlik, Sandy Feng, Bartosz Foroncewicz, Iman Francis, Michal Grat, Krzysztof Jurczyk, Goran Klintmalm, Maciej Krasnodebski, Geoff McCaughan, Rosa Miquel, Aldo Montano-Loza, Dilip Moonka, Krzysztof Mucha, Marek Myslak, Leszek Paczek, Agnieszka Perkowska-Ptasinska, Grzegorz Piecha, Trevor Reichman, Alberto Sanchez-Fueyo, Olga Tronina, Marta Wawrzynowicz-Syczewska, Andrzej Wiecek, Krzysztof Zieniewicz, Philip F. Halloran
Summary: This study analyzed gene expression in liver transplant biopsies to identify molecular changes associated with parenchymal injury, fibrosis, and steatohepatitis, offering potential insights into disease mechanisms for primary diseases. The findings suggest that molecular classifiers can predict histologic features with moderate accuracy, and pathways reflecting metabolic abnormalities were distinct from those associated with fibrosis. Overall, genome-wide assessment of liver transplant biopsies revealed complex molecular patterns associated with different aspects of liver disease.
AMERICAN JOURNAL OF TRANSPLANTATION
(2022)
Article
Gastroenterology & Hepatology
Michelle A. Wood-Trageser, Drew Lesniak, Alessandro Gambella, Kayla Golnoski, Sandy Feng, John Bucuvalas, Alberto Sanchez-Fueyo, A. Jake Demetris
Summary: The detection of immune pairs (iPAIRs) by next-generation pathology (NGP) can predict the failure of immunosuppression weaning in pediatric liver transplant recipients. The presence and importance of immune synapse formation in liver allografts have been confirmed, and it can be used to adjust immunosuppressive therapy and provide more information through gene analysis.
Article
Pathology
James B. Maurice, Akudo Nwaogu, Mahmoud Gouda, Olivia Shaw, Alberto Sanchez-Fueyo, Yoh Zen
Summary: This study aimed to examine the clinical utility and impact of the 2016 Banff criteria for acute antibody-mediated rejection (acute AMR) in patients with liver transplantation. The results showed that only a small percentage of DSA-positive patients met the Banff criteria for acute AMR, and combined acute AMR/TCMR cases were more common than isolated acute AMR.
Article
Gastroenterology & Hepatology
Tiong Y. Lim, Elena Perpinan, Maria-Carlota Londono, Rosa Miquel, Paula Ruiz, Ada S. Kurt, Elisavet Kodela, Amy R. Cross, Claudia Berlin, Joanna Hester, Fadi Issa, Abdel Douiri, Felix H. Volmer, Richard Taubert, Evangelia Williams, Anthony J. Demetris, Andrew Lesniak, Gilbert Bensimon, Juan Jose Lozano, Marc Martinez-Llordella, Tim Tree, Alberto Sanchez-Fueyo
Summary: This study investigated the role of low-dose IL-2 (LDIL-2) in maintaining liver allograft tolerance. The results showed that LDIL-2 expanded circulating regulatory T cells (Tregs) but failed to effectively suppress antigen-specific immune responses and promote the accumulation of intrahepatic Tregs. Furthermore, LDIL-2 induced a liver transcriptional response even before immunosuppression weaning. The study was terminated after the first 6 participants failed to reach the primary endpoint, requiring reinstitution of immunosuppression.
JOURNAL OF HEPATOLOGY
(2023)
Article
Immunology
Ada S. Kurt, Karoline Strobl, Paula Ruiz, Gabriel Osborn, Tonika Chester, Lauren Dawson, Karsten M. Warwas, Elizabeth H. Grey, Sotiris Mastoridis, Elisavet Kodela, Niloufar Safinia, Alberto Sanchez-Fueyo, Marc Martinez-Llordella
Summary: In this study, the phenotypic and functional characteristics of liver-resident Tregs in adult mice were explored, and their role in ameliorating liver inflammation and tissue damage was investigated. The results showed that the liver contained fewer resident Tregs compared to other tissues, and these Tregs had a distinct transcriptional profile. Animal experiments demonstrated that Tregs played a role in reducing liver inflammation, and strategies to increase the number of liver-resident Tregs significantly improved tissue damage. These findings offer insights into the immune network of liver-resident Tregs and suggest potential therapies for inflammatory liver diseases.
FRONTIERS IN IMMUNOLOGY
(2022)
Review
Gastroenterology & Hepatology
Aldo J. Montano-Loza, Manuel L. Rodriguez-Peralvarez, George-Philippe Pageaux, Alberto Sanchez-Fueyo, Sandy Feng
Summary: The outcomes of liver transplantation have improved over the years, but long-term survival rates are still lower than the general population. The liver has unique immunological functions and can modulate the recipient's immune system to promote tolerance. Immunosuppressive drugs should be individualized to control alloreactivity while minimizing toxicities.
JOURNAL OF HEPATOLOGY
(2023)
Article
Urology & Nephrology
C. Dudreuilh, P. Jarvis, N. Beadle, I Pilecka, O. Shaw, L. Gardner, C. Scotta, N. Mamode, D. S. Game, A. Sanchez-Fueyo, G. Lombardi, A. Learoyd, A. Douiri, A. Dorling
Summary: This study aims to suppress memory T and B cell responses against specific HLA antigens in highly sensitised kidney transplant patients by introducing autologous polyclonally expanded regulatory T cells. It is a two-part prospective clinical trial, with the first part being an observational phase and the second part being an interventional phase. The results will help determine the feasibility of using Treg therapy to modulate memory immune responses.
Meeting Abstract
Gastroenterology & Hepatology
Tiong Yeng Lim, Elena Perpinan, Maria Carlota Londono, Rosa Miquel, Paula Ruiz, Ada Kurt, Elisavet Codela, Amy Cross, Claudia Berlin, Joanna Hester, Fadi Issa, Abdel Douiri, Felix Volmer, Richard Taubert, Evangelia Williams, Jake Demetris, Andrew Lesniak, Gilbert Bensimon, Juanjo Lozano, Marc Martinez-Llordella, Timothy Tree, Alberto Sanchez-Fueyo
JOURNAL OF HEPATOLOGY
(2022)