Article
Materials Science, Multidisciplinary
De-Run Chen, Yuan Gao, Yao Xiao, Shu-Cheng Wan, Zhi-Zhong Wu, Shuo Wang, Xianbin Ma, Zhigang Xu, Zhi-Jun Sun
Summary: Regulating the immunosuppressive status of the tumor immune microenvironment is challenging. Pyroptosis shows potential in tumor immune therapy by recruiting immune cells. This study designed a nanogel-based prodrug to reshape tumor immunity, resulting in increased immune cell numbers and improved response rate to anti-PD-1 therapy.
APPLIED MATERIALS TODAY
(2022)
Article
Immunology
Sumedha Pareek, Alexandra S. Flegle, Drew Boagni, Jin Yong Kim, Dohyun Yoo, Abel Trujillo-Ocampo, Sung-Eun Lee, Mao Zhang, Sangyong Jon, Jin S. Im
Summary: This study found that post-transplantation treatment with bilirubin nanoparticles (BRNP) can reduce the occurrence of graft versus host disease (GVHD). BRNP can alleviate tissue damage, reduce inflammation, and regulate immune responses, thereby improving the clinical manifestations and survival rates of GVHD.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Engineering, Biomedical
Xueqian Wang, Beibei Wu, Yaqian Zhang, Xiaoqiu Dou, Changli Zhao, Chuanliang Feng
Summary: A supramolecular hydrogel platform based on chiral L-phenylalanine was developed, which was co-assembled with polydopamine nanoparticles (PDA-NPs) to prevent tumor relapse and promote wound healing. PDA-NPs enabled near-infrared light-triggered photothermal therapy and scavenged free radicals in surgical wounds. Chiral L-phenylalanine created a microenvironment that enhanced fibroblast adhesion, proliferation, and tissue regeneration. The antitumor effect was significantly enhanced by loading the anticancer drug doxorubicin (DOX) into the composite hydrogel.
ACTA BIOMATERIALIA
(2022)
Review
Immunology
Fathima A. Mohamed, Govindarajan Thangavelu, Stephanie Y. Rhee, Peter T. Sage, Roddy S. O'Connor, Jeffrey C. Rathmell, Bruce R. Blazar
Summary: The therapeutic efficacy of allo-HSCT is limited by the development of GVHD, with immune dysregulation leading to expansion of alloreactive cells and reduction in regulatory cells. New therapies are needed to restore the balance between effector and regulatory immune cells while preserving the beneficial graft-versus-tumor effect.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Aniket Ramshekar, Haibo Wang, Eric Kunz, Christian Pappas, Gregory S. Hageman, Brahim Chaqour, David B. Sacks, M. Elizabeth Hartnett
Summary: The study demonstrates that the binding of active Rap1 to the IQ domain of IQGAP1 is sufficient to interfere with active Rac1-mediated CEC activation and CNV formation. Activating Rap1 can reduce VEGF-mediated Rac1 activation and migration in CECs, as well as tube formation.
Review
Immunology
Hua Jiang, Denggang Fu, Alan Bidgoli, Sophie Paczesny
Summary: Allogeneic hematopoietic cell transplantation (allo-HCT) is crucial for treating hematological malignancies, but acute and chronic graft-versus-host disease (aGVHD and cGVHD) are major complications. Understanding the roles of T cell subsets in GVHD pathogenesis is essential for identifying new therapeutic targets and improving outcomes.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Immunology
Yiwen Liang, Jingyi Shen, Qiu Lan, Kexin Zhang, Yan Xu, Maxwell Duah, Kailin Xu, Bin Pan
Summary: This research found that PD-1 expression on T cells increased in mice with chronic graft-versus-host disease (cGVHD). Intervention of the PD-1/PD-L1 pathway showed a significant impact on the occurrence of cGVHD and graft-versus-tumor effect.
INTERNATIONAL IMMUNOPHARMACOLOGY
(2022)
Article
Multidisciplinary Sciences
Alejandro Schcolnik-Cabrera, Alma Chavez-Blanco, Guadalupe Dominguez-Gomez, Mandy Juarez, Ariana Vargas-Castillo, Rafael Isaac Ponce-Toledo, Donna Lai, Sheng Hua, Armando R. Tovar, Nimbe Torres, Delia Perez-Montiel, Jose Diaz-Chavez, Alfonso Duenas-Gonzalez
Summary: The combination of six drugs targeting tumor anabolism and host catabolism induces a quiescent energetic phenotype in cultured cancer cells, resulting in inhibition of tumor growth and reduced fat loss. The treatment is well-tolerated in mice and decreases whole animal energy expenditure.
SCIENTIFIC REPORTS
(2021)
Article
Medicine, Research & Experimental
Yuyi Wang, Ombretta Salvucci, Hidetaka Ohnuki, Andy D. Tran, Taekyu Ha, Jing-Xin Feng, Michael DiPrima, Hyeongil Kwak, Dunrui Wang, Yanlin Yu, Michael Kruhlak, Giovanna Tosato
Summary: SHP2 is essential for promoting endothelial cell survival and growth in tumor vasculature remodeling. Inhibiting SHP2 activity leads to reduced tumor growth and degeneration of tumor vasculature. Combination of SHP2 inhibitors with Ang2/TIE2 inhibitors shows promise in effectively targeting the tumor endothelium.
EMBO MOLECULAR MEDICINE
(2021)
Article
Gastroenterology & Hepatology
Caitlin B. Conboy, Jennifer A. Yonkus, Eee L. N. H. Buckarma, Dong-Gi Mun, Nathan W. Werneburg, Ryan D. Watkins, Roberto Alva-Ruiz, Jennifer L. Tomlinson, Yi Guo, Juan Wang, Daniel O'Brien, Chantal E. McCabe, Erik Jessen, Rondell P. Graham, Rogier C. Buijsman, Diep Vu, Jos de Man, Sumera I. Ilyas, Mark J. Truty, Mitesh Borad, Akhilesh Pandey, Gregory J. Gores, Rory L. Smoot
Summary: A novel LCK inhibitor, NTRC 0652-0, was found to inhibit YAP signaling in CCA cells. It decreased tyrosine phosphorylation, nuclear localization, and co-transcriptional activity of YAP, leading to apoptotic cell death in CCA cell lines. FGFR2 fusion-positive CCA was identified as a susceptible subset, and NTRC 0652-0 showed preclinical efficacy in patient-derived organoid and xenograft models.
JOURNAL OF HEPATOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Wineke Bakker, Calinda K. E. Dingenouts, Kirsten Lodder, Karien C. Wiesmeijer, Alwin de Jong, Kondababu Kurakula, Hans-Jurgen J. Mager, Anke M. Smits, Margreet R. de Vries, Paul H. A. Quax, Marie Jose T. H. Goumans
Summary: In HHT1, deficiency of endoglin leads to immune cell imbalance, particularly an excessive increase in inflammatory macrophages, which hinders tissue repair. Inhibiting BMP signaling restores macrophage balance and improves tissue repair after ischemic injury.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Chemistry, Medicinal
Meganathan Nandakumar, Anja Ollodart, Neil Fleck, Nirav R. Kapadia, Andrew Frando, Vishant Boradia, Jeffery L. Smith, Junxi Chen, William J. Zuercher, Timothy M. Willson, Christoph Grundner
Summary: A new compound called pyrrolopyrimidine (43) has been discovered in this study, which has the potential to prevent drug resistance by inhibiting both nonreplicating Mtb and a host kinase.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Review
Biochemistry & Molecular Biology
Eugene Appenteng Osae, Philipp Steven
Summary: Despite extensive experience with hematopoietic stem cell transplantation, achieving stable ocular health post-transplantation remains a challenge due to the high occurrence of ocular graft-versus-host disease (oGvHD). Limited understanding of oGvHD pathophysiology, especially the involvement of the meibomian gland, highlights the need for additional preclinical models and research on this condition.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Immunology
Melrine Pereira, Natasha Ting Lee, Jonathan Noonan, Abbey E. H. Willcox, Ilaria Calvello, Smitha Rose Georgy, Carly Selan, Joanne S. Chia, Wayne Hauw, Xiaowei Wang, Karlheinz Peter, Simon C. Robson, Harshal H. Nandurkar, Maithili Sashindranath
Summary: Allogenic hematopoietic stem cell transplant can result in sinusoidal obstruction syndrome and graft-versus-host disease. Endothelial activation is an early sign of acute GvHD and SOS in a clinically relevant mouse model based on myeloablative chemotherapy. Preventing endothelial activation may be a viable therapeutic strategy to prevent GvHD.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Multidisciplinary Sciences
Peter J. Mullen, Gustavo Garcia, Arunima Purkayastha, Nedas Matulionis, Ernst W. Schmid, Milica Momcilovic, Chandani Sen, Justin Langerman, Arunachalam Ramaiah, David B. Shackelford, Robert Damoiseaux, Samuel W. French, Kathrin Plath, Brigitte N. Gomperts, Vaithilingaraja Arumugaswami, Heather R. Christofk
Summary: This study revealed that SARS-CoV-2 infection alters host cell metabolism by increasing glucose entry into the TCA cycle and reducing oxidative glutamine metabolism. Additionally, infection with SARS-CoV-2 activates mTORC1, and inhibiting mTORC1 can suppress viral replication in kidney epithelial cells and lung ALI cultures. These findings suggest that targeting mTORC1 could be a potential treatment strategy for COVID-19 patients.
NATURE COMMUNICATIONS
(2021)
Article
Hematology
Nico Gagelmann, Gerald Georg Wulf, Johannes Duell, Bertram Glass, Pearl van Heteren, Bastian von Tresckow, Monika Fischer, Olaf Penack, Francis Ayuk, Herrmann Einsele, Udo Holtick, Julia Thomson, Peter Dreger, Nicolaus Kroeger
Summary: Hematotoxicity after CAR-T therapy can be managed with hematopoietic stem cell boost (HSCB), which showed a quick response and improved outcomes for sustained moderate to severe neutropenia. 31 patients received HSCB, with an overall neutrophil response rate of 84% and a median response time of 9 days. Patients with shorter duration of neutropenia had significantly better survival outcomes compared to those with longer duration. The 1-year overall survival rate was 59%.
Article
Hematology
Feiyan Mo, Norihiro Watanabe, Kayleigh I. Omdahl, Phillip M. Burkhardt, Xiaoyun Ding, Eiko Hayase, Angela Panoskaltsis-Mortari, Robert R. Jenq, Helen E. Heslop, Leslie S. Kean, Malcolm K. Brenner, Victor Tkachev, Maksim Mamonkin
Summary: OX40 plays a central role in aGVHD by regulating activation and expansion of T cells. Researchers have developed a specific OX40 cytotoxic receptor that selectively eliminates OX40-positive T cells, reducing the occurrence of aGVHD. Furthermore, combining OX40 targeting with leukemia-specific chimeric antigen receptor provides simultaneous protection against leukemia and aGVHD in post-transplant residual disease.
Article
Hematology
Benjamin Diamond, Bachisio Ziccheddu, Kylee Maclachlan, Justin Taylor, Eileen Boyle, Juan Arango Ossa, Jacob Jahn, Maurizio Affer, Tulasigeri M. Totiger, David Coffey, Namrata Chandhok, Justin Watts, Luisa Cimmino, Sydney X. Lu, Niccolo Bolli, Kelly Bolton, Heather Landau, Jae H. Park, Karuna Ganesh, Andrew McPherson, Mikkael A. Sekeres, Alexander Lesokhin, David J. Chung, Yanming Zhang, Caleb Ho, Mikhail Roshal, Jeffrey Tyner, Stephen Nimer, Elli Papaemmanuil, Saad Usmani, Gareth Morgan, Ola Landgren, Francesco Maura
Summary: Through genomic sequencing of 39 therapy-related myeloid malignancies, it was discovered that chemotherapy can accelerate the evolution of cancer cells by inducing mutations and DNA damage. Preleukemic clones (clonal hematopoiesis, CH) that exist before chemotherapy can acquire complex events and genomic drivers after chemotherapy, leading to the development of therapy-related myeloid neoplasms.
Article
Public, Environmental & Occupational Health
Erica J. Rayack, Hibah Mahwish Askari, Elissa Zirinsky, Sarah Lapidus, Hassan Sheikha, Chikondi Peno, Yasaman Kazemi, Devyn Yolda-Carr, Chen Liu, Nathan D. Grubaugh, Albert I. Ko, Anne L. Wyllie, Erica S. Spatz, Carlos R. Oliveira, Amy K. Bei
Summary: In the early phase of the COVID-19 pandemic, a PCR-based COVID-19 surveillance program was established in childcare facilities to collect actionable public health data and aid in the resumption of standard operations. This study describes the development of a saliva testing program for children and childcare center staff, providing a feasible method of asymptomatic screening and symptomatic testing. The study emphasizes the importance of cooperation between childcare centers, parents/guardians, and staff to mitigate COVID-19 transmission.
FRONTIERS IN PUBLIC HEALTH
(2023)
Article
Hematology
Peter Bader, Claudia Rossig, Martin Hutter, Francis Ayuketang Ayuk, Claudia D. Baldus, Veit L. Buecklein, Halvard Bonig, Gunnar Cario, Hermann Einsele, Udo Holtick, Christian Koenecke, Shahrzad Bakhtiar, Annette Kuenkele, Roland Meisel, Fabian Mueller, Ingo Mueller, Olaf Penack, Eva Rettinger, Martin G. Sauer, Paul -Gerhardt Schlegel, Jan Soerensen, Arend von Stackelberg, Brigitte Strahm, Julia Hauer, Tobias Feuchtinger, Andrea Jarisch
Summary: This retrospective study investigated the efficacy of Tisa-cel in 81 patients with pB-ALL. The results showed that CAR T cell therapy can effectively alleviate the disease, with a 2-year survival rate of 45.3%. Importantly, patients who relapsed after 6 months post-allo-HSCT had a higher survival rate, which provides valuable information for clinical decision-making.
Article
Hematology
Kylee H. Maclachlan, Tina Bagratuni, Efstathios Kastritis, Bachisio Ziccheddu, Sydney Lu, Venkata Yellapantula, Chris Famulare, Kimon Argyropoulos, Andriy Derkach, Elli Papaemmanuil, Ahmet Dogan, Alexander Lesokhin, Saad Z. Usmani, C. Ola Landgren, Lia M. Palomba, Francesco Maura, Meletios A. Dimopoulos
Summary: The genomic landscape of Waldenstrom macroglobulinemia (WM) is characterized by MYD88 somatic mutations which are present from precursor stages. Analysis shows sustained activity of germinal center (GC) mutational signatures, suggesting continued interaction between WM and GC. Copy number aberrations (CNA) progressively increase in symptomatic WM and relapsed disease, with MYD88 wild-type cases often demonstrating early chromosomal gains and later subclonal CNA changes. This suggests that CNA may contribute to progression risk from precursor conditions to symptomatic disease.
Article
Biology
David Ascheid, Magdalena Baumann, Caroline Funke, Julia Volz, Juergen Pinnecker, Mike Friedrich, Marie Hoehn, Rajender Nandigama, Sueleyman Erguen, Bernhard Nieswandt, Katrin G. Heinze, Erik Henke
Summary: In tumor therapy, anti-angiogenic approaches can improve the efficacy of subsequently or co-administered drugs by normalizing the defective tumor blood vessels. A comprehensive evaluation of the vascular network using high-resolution angiographic images can effectively assess the degree of disorganization in different tumor entities and predict the potential reversal under therapeutic treatment.
Review
Oncology
Florent Malard, Robert R. Jenq
Summary: Allogeneic hematopoietic cell transplantation (alloHCT) is a standard therapy for hematological diseases. Recent studies have shown that the composition of intestinal microbiota is strongly associated with outcomes such as graft-versus-host disease (GVHD). Modulating the microbiota has the potential to improve clinical outcomes.
Article
Gastroenterology & Hepatology
Cameron Beech, Chen Liu, Xuchen Zhang
CLINICS IN LIVER DISEASE
(2023)
Article
Oncology
Nicola Giesen, Elena Busch, Enrico Schalk, Gernot Beutel, Maria M. Ruethrich, Marcus Hentrich, Bernd Hertenstein, Hans H. Hirsch, Meinolf Karthaus, Yascha Khodamoradi, Philipp Koehler, William Kruger, Michael Koldehoff, Robert Krause, Sibylle C. Mellinghoff, Olaf Penack, Michael Sandherr, Ruth SeggeWiss-Bernhardt, Karsten Spiekermanny, Rosanne Sprute, Jannik Stemler, Florian Weissinger, Bernhard Woermann, Hans-Heinrich Wolf, Oliver A. Cornely, Christina T. Rieger, Marie von Lilienfeld-Toal
Summary: The novel coronavirus SARS-CoV-2 and associated infectious disease COVID-19 present a significant challenge to healthcare systems worldwide, with cancer patients being identified as a high-risk population. The rapid development of vaccines and therapeutic agents against COVID-19 offers new options for improving care and protection of cancer patients. However, ongoing epidemiological changes and the emergence of new virus variants require constant revisions and adaptations of prophylaxis and treatment strategies to address these new challenges.
EUROPEAN JOURNAL OF CANCER
(2023)
Review
Infectious Diseases
Jannik Stemler, Sibylle C. Mellinghoff, Yascha Khodamoradi, Rosanne Sprute, Annika Y. Classen, Sonja E. Zapke, Martin Hoenigl, Robert Krause, Martin Schmidt-Hieber, Werner J. Heinz, Michael Klein, Philipp Koehler, Blasius Liss, Michael Koldehoff, Christoph Buhl, Olaf Penack, Georg Maschmeyer, Enrico Schalk, Cornelia Lass-Floerl, Meinolf Karthaus, Markus Ruhnke, Oliver A. Cornely, Daniel Teschner
Summary: Patients with haematological malignancies are at high risk of invasive fungal disease. The German Society of Haematology and Medical Oncology has updated their antifungal prophylaxis recommendations, recommending continued antifungal prophylaxis for patients with long-lasting neutropenia and posaconazole as the drug of choice. There is insufficient data to give general recommendations for antifungal prophylaxis in patients receiving novel treatments for HM, such as CAR-T-cell therapy or novel targeted therapies for AML.
JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY
(2023)
Article
Biochemistry & Molecular Biology
Christoph K. Stein-Thoeringer, Neeraj Y. Saini, Eli Zamir, Viktoria Blumenberg, Maria-Luisa Schubert, Uria Mor, Matthias A. Fante, Sabine Schmidt, Eiko Hayase, Tomo Hayase, Roman Rohrbach, Chia-Chi Chang, Lauren McDaniel, Ivonne Flores, Rogier Gaiser, Matthias Edinger, Daniel Wolff, Martin Heidenreich, Paolo Strati, Ranjit Nair, Dai Chihara, Luis E. Fayad, Sairah Ahmed, Swaminathan P. Iyer, Raphael E. Steiner, Preetesh Jain, Loretta J. Nastoupil, Jason Westin, Reetakshi Arora, Michael L. Wang, Joel Turner, Meghan Menges, Melanie Hidalgo-Vargas, Kayla Reid, Peter Dreger, Anita Schmitt, Carsten Mueller-Tidow, Frederick L. Locke, Marco L. Davila, Richard E. Champlin, Christopher R. Flowers, Elizabeth J. Shpall, Hendrik Poeck, Sattva S. Neelapu, Michael Schmitt, Marion Subklewe, Michael D. Jain, Robert R. Jenq, Eran Elinav
Summary: Evidence suggests that the gut microbiome may influence the effectiveness of cancer immunotherapy. In a cohort of B cell lymphoma patients from Germany and the United States, it was found that the use of broad-spectrum antibiotics prior to CAR-T cell therapy was associated with negative outcomes. Additionally, certain microbiome features were found to be correlated with the survival and progression of lymphoma in these patients.
Article
Oncology
Katherine Knorr, Jahan Rahman, Caroline Erickson, Eric Wang, Mara Monetti, Zhuoning Li, Juliana Ortiz-Pacheco, Andrew Jones, Sydney X. Lu, Robert F. Stanley, Maria Baez, Nina Fox, Cynthia Castro, Alessandra E. Marino, Caroline Jiang, Alex Penson, Simon J. Hogg, Xiaoli Mi, Hideaki Nakajima, Hiroyoshi Kunimoto, Koutarou Nishimura, Daichi Inoue, Benjamin Greenbaum, David Knorr, Jeffrey Ravetch, Omar Abdel-Wahab
Summary: Despite recent advances in AML treatment, targeting surface antigens in AML remains challenging due to shared expression across malignant and normal cells. This study identified unique expression of RNA helicase U5 snRNP200 on AML cells but not on normal hematopoietic precursors, as well as skewed Fc receptor distribution in the AML immune microenvironment. Anti-U5 snRNP200 antibodies engaging activating Fc receptors showed efficacy in AML models and were enhanced by combination with azacitidine.
Article
Hematology
Veit Buecklein, Ariel Perez, Kai Rejeski, Gloria Iacoboni, Vindi Jurinovic, Udo Holtick, Olaf Penack, Soraya Kharboutli, Viktoria Blumenberg, Josephine Ackermann, Lisa Froelich, Grace Johnson, Kedar Patel, Brian Arciola, Rahul Mhaskar, Anthony Wood, Christian Schmidt, Omar Albanyan, Philipp Goedel, Eva Hoster, Lars Bullinger, Andreas Mackensen, Frederick Locke, Michael Von Bergwelt, Pere Barba, Marion Subklewe, Michael D. Jain
Summary: Real-world evidence shows that patients receiving CD19 chimeric antigen receptor (CAR) T-cell therapy in Europe and with tisagenlecleucel have lower survival rates. The reasons for these discrepancies, including logistic and patient-and disease-related factors, are not well understood.
Article
Statistics & Probability
Yushu Shi, Liangliang Zhang, Kim-Anh Do, Robert Jenq, Christine B. Peterson
Summary: There is a strong interest in analyzing the variations in the microbiome among cancer patients to determine its importance in treatment outcomes. In this study, a novel unsupervised clustering approach in the Bayesian framework is proposed to identify subgroups of patients with similar microbiome profiles. The approach improves upon existing model-based clustering methods by incorporating feature selection, determining the appropriate number of clusters from the data, and integrating tree structure information. The performance of the proposed method is compared to existing methods using simulated data and applied to a clinical study on pancreatic cancer patients' tumor microbiome.
JOURNAL OF THE ROYAL STATISTICAL SOCIETY SERIES C-APPLIED STATISTICS
(2023)