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Blockade of TREM2 ameliorates pulmonary inflammation and fibrosis by modulating sphingolipid metabolism.
Transl Res
January 2025
Department of Respiratory and Critical Care Medicine, Beijing Institute of Respiratory Medicine, Beijing Chao-Yang Hospital, Capital Medical University, Beijing 100020, China; Beijing Research Center for Respiratory Infectious Diseases, Beijing 100020, China; Medical Research Center, Beijing Institute of Respiratory Medicine, Beijing Chao-Yang Hospital, Capital Medical University, Beijing 100020, China. Electronic address:
Pulmonary fibrosis is a chronic interstitial lung disease involving systemic inflammation and abnormal collagen deposition. Dysregulations in lipid metabolism, such as macrophage-dependent lipid catabolism, have been recognized as critical factors for the development of pulmonary fibrosis. However, little is known about the signaling pathways involved and the key regulators.
View Article and Find Full Text PDFA tumor-conditional IL-15 safely synergizes with immunotherapy to enhance antitumor immune responses.
Mol Ther
December 2024
Engineering Research Center of Cell and Therapeutic Antibody, Ministry of Education, School of Pharmacy, Shanghai Jiao Tong University, 800 Dongchuan Road, Shanghai 200240, China; Shanghai Frontiers Science Center for Drug Target Identification and Delivery, National Key Laboratory of Innovative Immunotherapy, School of Pharmacy, Shanghai Jiao Tong University, 800 Dongchuan Road, Shanghai 200240, China; Chongqing Research Institute, Shanghai Jiao Tong University, Chongqing 401135, China. Electronic address:
It is a challenge to invigorate tumor-infiltrating lymphocytes without causing immune-related adverse events, which also stands as a primary factor contributing to resistance against cancer immunotherapies. Interleukin (IL)-15 can potently promote expansion and activation of T cells, but its clinical use has been limited by dose-limiting toxicities. In this study, we develop a tumor-conditional IL-15 (pro-IL-15), which masks IL-15 with steric hindrance caused by Fc fragment and IL-15Rα-sushi domain.
View Article and Find Full Text PDFA machine learning model reveals expansive downregulation of ligand-receptor interactions that enhance lymphocyte infiltration in melanoma with developed resistance to immune checkpoint blockade.
Nat Commun
October 2024
Cancer Data Science Laboratory (CDSL), Center for Cancer Research (CCR), National Cancer Institute (NCI), National Institutes of Health (NIH), Bethesda, MD, USA.
Immune checkpoint blockade (ICB) is a promising cancer therapy; however, resistance frequently develops. To explore ICB resistance mechanisms, we develop Immunotherapy Resistance cell-cell Interaction Scanner (IRIS), a machine learning model aimed at identifying cell-type-specific tumor microenvironment ligand-receptor interactions relevant to ICB resistance. Applying IRIS to deconvolved transcriptomics data of the five largest melanoma ICB cohorts, we identify specific downregulated interactions, termed resistance downregulated interactions (RDI), as tumors develop resistance.
View Article and Find Full Text PDFReduction of myeloid-derived suppressor cells in prostate cancer murine models and patients following white button mushroom treatment.
Clin Transl Med
October 2024
Department of Cancer Biology & Molecular Medicine, Beckman Research Institute, City of Hope, Duarte, California, USA.
Background: In a previously reported Phase I trial, we observed therapy-associated declines in circulating myeloid-derived suppressor cells (MDSCs) with the administration of white button mushroom (WBM) tablets in prostate cancer (PCa) patients. These observations led us to hypothesise that WBM could mitigate PCa progression by suppressing MDSCs.
Methods: We performed bidirectional translational research to examine the immunomodulatory effects of WBM consumption in both syngeneic murine PCa models and patients with PCa participating in an ongoing randomised Phase II trial (NCT04519879).
Harnessing the Power of NK Cell Receptor Engineering as a New Prospect in Cancer Immunotherapy.
Pharmaceutics
August 2024
Pharmaceutics Division, Faculty of Science, Utrecht Institute for Pharmaceutical Sciences (UIPS), Utrecht University, Universiteitsweg 99, 3584 CG Utrecht, The Netherlands.
Natural killer (NK) cells have recently gained popularity as an alternative for cancer immunotherapy. Adoptive cell transfer employing NK cells offers a safer therapeutic option compared to T-cell-based therapies, due to their significantly lower toxicity and the availability of diverse autologous and allogeneic NK cell sources. However, several challenges are associated with NK cell therapies, including limited in vivo persistence, the immunosuppressive and hostile tumor microenvironment (TME), and the lack of effective treatments for solid tumors.
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