Review
Medicine, Research & Experimental
Yuan-Tong Liu, Zhi-Jun Sun
Summary: Immunotherapy, particularly through immune checkpoint inhibitors, has significantly improved the treatment of malignant tumors by enhancing T cell infiltration into tumors. Understanding the mechanisms underlying cold tumors, which lack T cell infiltration, is crucial to improving immunotherapy efficacy. Strategies to transform cold tumors into hot tumors and increase T cell infiltration are discussed, along with the potential of nanomedicines in enhancing tumor immunotherapy.
Article
Multidisciplinary Sciences
Fotis Nikolos, Kazukuni Hayashi, Xen Ping Hoi, Mark Ellie Alonzo, Qianxing Mo, Armine Kasabyan, Hideki Furuya, Jane Trepel, Dolores Di Vizio, Jlenia Guarnerio, Dan Theodorescu, Charles Rosser, Andrea Apolo, Matthew Galsky, Keith Syson Chan
Summary: Chemoimmunotherapy has shown limited clinical benefit in bladder cancer patients and the reasons for this are not well understood. This study reveals that platinum-based chemotherapy hinders the infiltration and activity of CD8+ T cells in mouse models of muscle-invasive bladder cancer. The release of prostaglandin E-2 (PGE(2)) from dying cancer cells is identified as a mechanism that inhibits dendritic cell maturation. By blocking PGE(2) release, CD8+ T cells regain their tumoricidal activity and infiltrate the tumor site. Blocking PGE(2) release synergizes with chemotherapy and enhances the response to immune checkpoint inhibitor therapy. These findings highlight the potential of targeting the COX-2/PGE2 axis in chemoimmunotherapy for bladder cancer.
NATURE COMMUNICATIONS
(2022)
Review
Immunology
Mengjie Liang, Xingzhou Wang, Daming Cai, Wenxian Guan, Xiaofei Shen
Summary: Tissue-resident memory T cells (Trm) are a specific subgroup of T cells that reside in tissues and are the most abundant memory T cell population in various tissues. They can be activated locally by infection or tumor cells and rapidly eliminate them to restore local immunostasis in gastrointestinal tissues. It has been found that tissue-resident memory T cells have great potential to combat gastrointestinal tumors, making them promising immune markers for immunotherapy and potential targets for cell therapy. This review comprehensively explores the role of tissue-resident memory T cells in gastrointestinal tumors and discusses their future prospects in immunotherapy, aiming to provide insights for clinical applications.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Pharmacology & Pharmacy
J. Timothy Prior, Christopher Davitt, Jonathan Kurtz, Patrick Gellings, James B. McLachlan, Lisa A. Morici
Summary: OMVs have the potential to function as a stand-alone adjuvant, driving stronger immune responses compared to heat-inactivated and live-attenuated bacteria. They induce robust humoral and cellular immune responses, generating stronger antibody and B cell responses than traditional adjuvants, while remaining unaffected by pre-existing antibodies.
Review
Immunology
Kyle J. Bednar, Jee Ho Lee, Tatiana Ort
Summary: CD4 (+) CD25 (high) Foxp3 (+) regulatory T-cells (Tregs) play a crucial role in maintaining immune homeostasis and tolerance. This review summarizes the concept of Treg cell stability and plasticity, as well as the underlying molecular mechanisms, including translational and epigenetic regulators, which may contribute to the development of new therapeutic strategies.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Engineering, Biomedical
Wenyan Fu, Changhai Lei, Chuqi Wang, Zetong Ma, Tian Li, Fangxing Lin, Ruixue Mao, Jian Zhao, Shi Hu
Summary: Synthetically generated and clonally expanded libraries of immune cells displaying diverse repertoires of chimaeric antigen receptors lead to long-lasting and potent antitumour responses in mouse models of epithelial tumours, providing possibilities for the discovery of new CARs and the development of immunotherapies.
NATURE BIOMEDICAL ENGINEERING
(2022)
Review
Immunology
Brigette C. Duckworth, Joanna R. Groom
Summary: The relationship between the extrinsic environment and the internal transcriptional network is circular in T cells. Naive T cells engage with antigen-presenting cells to set transcriptional differentiation networks in motion, which regulates migration and differentiation programming. Differentiation programs for CD4+ T-FH and CD8+ T-SCM cells are compared and contrasted with their effector counterparts, T-H1 and T-SLEC cells, to understand T cell differentiation and effector function.
IMMUNOLOGICAL REVIEWS
(2021)
Review
Immunology
Xinyu Gu, Qingfei Chu, Xiao Ma, Jing Wang, Chao Chen, Jun Guan, Yanli Ren, Shanshan Wu, Haihong Zhu
Summary: NKT cells play a crucial role in the immune system, particularly in liver diseases. Hepatic iNKT cells interact with other immune cells through direct cell-to-cell contact and cytokine secretion, bridging the innate and adaptive immune systems.
FRONTIERS IN IMMUNOLOGY
(2022)
Review
Oncology
Tara Arvedson, Julie M. Bailis, Carolyn D. Britten, Matthias Klinger, Dirk Nagorsen, Angela Coxon, Jackson G. Egen, Flavius Martin
Summary: T cell engagers (TCEs) are promising immunotherapies that redirect T cells for tumor killing. While successful in hematologic malignancies, the clinical development of TCEs in solid tumors faces challenges and requires consideration of multiple factors. This review summarizes the history of blinatumomab, lessons from TCEs in hematologic malignancies, and recent trials in solid tumors. The approaches to improve the efficacy and safety of TCEs in solid tumors, including combination therapies, are discussed.
ANNUAL REVIEW OF CANCER BIOLOGY
(2022)
Review
Oncology
Marit M. Melssen, Natasha D. Sheybani, Katie M. Leick, Craig L. Slingluff Jr
Summary: Increased immune cell infiltration into tumors is associated with improved patient survival and predicts response to immune therapies. Thus, identification of factors that determine the extent of immune infiltration is crucial, so that methods to intervene on these targets can be developed.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2023)
Article
Biology
Yariv Greenshpan, Omri Sharabi, Aner Ottolenghi, Avishag Cahana, Kiran Kundu, Ksenia M. Yegodayev, Moshe Elkabets, Roi Gazit, Angel Porgador
Summary: The authors investigate the use of synthetic promoters based on IFN-gamma, TNF alpha, and hypoxia responsive elements to regulate gene expression in the context of chimeric antigen expression (CAR), suggesting that this approach can enhance safety and specificity of CAR T cells in the tumor microenvironment.
COMMUNICATIONS BIOLOGY
(2021)
Article
Orthopedics
Kosei Nakajima, Abraham Raz
Summary: This study found that T-cell infiltration levels varied in musculoskeletal tumors, with CD3E and CD8A expressions being predominantly inhibited in certain tumors. CD4 expression was upregulated in a few tumor types like chondrosarcoma and giant cell tumor of bone, while other tumors showed lower expressions. Overall, musculoskeletal tumors may be defined as immune-quiescent tumors, and targeting Galectin-3 and/or immune-infiltrative agents could be crucial in these immunologically noninflamed tumors to accelerate immunotherapeutic response.
JOURNAL OF ORTHOPAEDIC RESEARCH
(2021)
Review
Medicine, General & Internal
Mengting Ding, Jiaxing Lin, Caipeng Qin, Ping Wei, Jiahe Tian, Tianxin Lin, Tao Xu
Summary: This review discusses the innovative applications of synthetic biology in the clinical diagnosis and treatment of bladder cancer, including the utilization of genetic elements to regulate gene expression, the design of gene circuits to distinguish cancer cells from normal cells, genetically modified T cells for targeted attacks, and synthetic nanomaterials for detecting and killing BC cells.
CHINESE MEDICAL JOURNAL
(2022)
Article
Biotechnology & Applied Microbiology
Antonio E. Barberio, Sean G. Smith, Ivan S. Pires, Sonia Iyer, Ferenc Reinhardt, Mariane B. Melo, Heikyung Suh, Robert A. Weinberg, Darrell J. Irvine, Paula T. Hammond
Summary: Ovarian cancer is difficult to treat and has been resistant to immunotherapies. However, a new study shows that systemically delivered nanoparticles can effectively target and engage the immune system as a treatment in multiple ovarian tumor models, including those with low immune response. This therapy demonstrates reduced toxicity and maintained anti-tumor efficacy, resulting in a 30% complete survival rate.
BIOENGINEERING & TRANSLATIONAL MEDICINE
(2023)
Review
Immunology
Hamed Fouladseresht, Atefe Ghamar Talepoor, Nahid Eskandari, Marzieh Norouzian, Behrooz Ghezelbash, Mohammad Reza Beyranvand, Seyed Aria Nejadghaderi, Kristin Carson-Chahhoud, Ali-Asghar Kolahi, Saeid Safiri
Summary: This study aims to compare the similarities and differences in common inflammatory mediators, cytokines, and immune cell subtypes between patients with COVID-19 and trauma. By understanding these kinetic characteristics, it is possible to more accurately predict the prognosis of COVID-19 and intervene accordingly.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Multidisciplinary Sciences
Erin Barnhart, Kun-Chun Lee, Greg M. Allen, Julie A. Theriot, Alex Mogilner
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2015)
Meeting Abstract
Oncology
Hersh Kumar Bhargava, Patrick Leo, Robin Elliott, Andrew Janowczyk, Jon Whitney, Sanjay Gupta, Kosj Yamoah, Timothy Rebbeck, Michael D. Feldman, Priti Lal, Anant Madabhushi
JOURNAL OF CLINICAL ONCOLOGY
(2018)
Article
Pathology
Aileen Grace P. Arriola, Sahar J. Farahani, Hersh K. Bhargava, Thomas J. Guzzo, John S. J. Brooks, Priti Lal
AMERICAN JOURNAL OF CLINICAL PATHOLOGY
(2019)
Article
Genetics & Heredity
Lutz Kockel, Catherine Griffin, Yaseen Ahmed, Lauren Fidelak, Arjun Rajan, Ethan P. Gould, Myles Haigney, Benjamin Ralston, Rex J. Tercek, Lara Galligani, Sagar Rao, Lutfi Huq, Hersh K. Bhargava, Ailis C. Dooner, Emily G. Lemmerman, Ruby F. Malusa, Tran H. Nguyen, Julie S. Chung, Sara M. Gregory, Kiyomasa M. Kuwana, Jonathan T. Regenold, Alexander Wei, Jake Ashton, Patrick Dickinson, Kate Martel, Connie Cai, Carissa Chen, Stephen Price, Jeffrey Qiao, David Shepley, Joanna Zhang, Meghana Chalasani, Khanh Nguyen, August Aalto, ByungJun Kim, Erik Tazawa-Goodchild, Amanda Sherwood, Ahmad Rahman, Sum Ying Celeste Wu, Joel Lotzkar, Serena Michaels, Hillary Aristotle, Antigone Clark, Grace Gasper, Evan Xiang, Frieda Luna Schlor, Melissa Lu, Kate Haering, Julia Friberg, Alyssa Kuwana, Jonathan Lee, Alan Liu, Emma Norton, Leena Hamad, Clara Lee, Dara Okeremi, Harry diTullio, Kat Dumoulin, Sun Yu Gordon Chi, Grayson S. Derossi, Rose E. Horowitch, Elias C. Issa, Dan T. Le, Bryce C. Morales, Ayush Noori, Justin Shao, Sophia Cho, Mai N. Hoang, Ian M. Johnson, Katherine C. Lee, Maria Lee, Elizabeth A. Madamidola, Katrina E. Schmitt, Gabriel Byan, Taeyoung Park, Jonathan Chen, Alexi Monovoukas, Madison J. Kang, Tanner McGowan, Joseph J. Walewski, Brennan Simon, Sophia J. Zu, Gregory P. Miller, Kate B. Fitzpatrick, Nicole Lantz, Elizabeth Fox, Jeanette Collette, Richard Kurtz, Chris Duncan, Ryan Palmer, Cheryl Rotondo, Eric Janicki, Townley Chisholm, Anne Rankin, Sangbin Park, Seung K. Kim
G3-GENES GENOMES GENETICS
(2019)
Article
Biochemistry & Molecular Biology
Jaline Gerardin, Nishith R. Reddy, Wendell A. Lim
Article
Oncology
Hersh K. Bhargava, Patrick Leo, Robin Elliott, Andrew Janowczyk, Jon Whitney, Sanjay Gupta, Pingfu Fu, Kosj Yamoah, Francesca Khani, Brian D. Robinson, Timothy R. Rebbeck, Michael Feldman, Priti Lal, Anant Madabhushi
CLINICAL CANCER RESEARCH
(2020)
Article
Multidisciplinary Sciences
Hersh K. Bhargava, Keisuke Tabata, Jordan M. Byck, Maho Hamasaki, Daniel P. Farrell, Ivan Anishchenko, Frank DiMaio, Young Jun Im, Tamotsu Yoshimori, James H. Hurley
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2020)
Article
Multidisciplinary Sciences
Jasper Z. Williams, Greg M. Allen, Devan Shah, Igal S. Sterin, Ki H. Kim, Vivian P. Garcia, Gavin E. Shavey, Wei Yu, Cristina Puig-Saus, Jennifer Tsoi, Antoni Ribas, Kole T. Roybal, Wendell A. Lim
Article
Biochemistry & Molecular Biology
Claire Deo, Ahmed S. Abdelfattah, Hersh K. Bhargava, Adam J. Berro, Natalie Falco, Helen Farrants, Benjamien Moeyaert, Mariam Chupanova, Luke D. Lavis, Eric R. Schreiter
Summary: Functional imaging in biology has been revolutionized by the use of fluorescent indicators, but there is a need for additional sensor scaffolds with properties such as bright, far-red emission. This study introduces a new platform for 'chemigenetic' fluorescent indicators using self-labeling HaloTag protein conjugated to synthetic fluorophores, enabling the creation of highly tunable calcium and voltage sensors with bright, far-red emission.
NATURE CHEMICAL BIOLOGY
(2021)
Article
Multidisciplinary Sciences
Kyle G. Daniels, Shangying Wang, Milos S. Simic, Hersh K. Bhargava, Sara Capponi, Yurie Tonai, Wei Yu, Simone Bianco, Wendell A. Lim
Summary: This study constructed a CAR library containing synthetic costimulatory domains and used neural networks and machine learning to decode the combinatorial grammar of CAR signaling motifs. Non-native combinations of signaling motifs were found to enhance cytotoxicity and stemness associated with tumor killing.
Review
Oncology
Greg M. Allen, Wendell A. Lim
Summary: In the past, cancer therapeutics focused on precision targeting of single cancer-associated molecules, which still had limitations. However, the recent development of cell-based therapies, equipped with synthetic circuits, presents a revolutionary opportunity to target cancers in a more precise and effective way. Moreover, combining these smart cell engineering capabilities with machine learning analysis of genomic data could enhance tumor recognition and prevent tumor escape.
NATURE REVIEWS CANCER
(2022)