ArticleJournal of experimental & clinical cancer research : CR2023
Lysosome blockade induces divergent metabolic programs in macrophages and tumours for cancer immunotherapy.
Article in Journal of experimental & clinical cancer research : CR, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 15 citations in OpenAlex.
- Migration of immune cells in tumors and inflammation: molecular mechanisms and therapeutic targets.Signal transduction and targeted therapy · 2026Review
- Compartmental pH regulation in cancer and antitumor immunity: therapeutic opportunities and challenges.Apoptosis : an international journal on programmed cell death · 2026Review
- Morpho-functional plasticity of tumour-associated macrophages: linking cell shape, ultrastructure, and immune regulation in cancer.Clinical and experimental medicine · 2026Review
- CLN7 suppression induces apoptosis via mTOR-regulated and chaperone-mediated autophagy in myeloid leukemia cells.Cell death & disease · 2026Article
- Immunocyte reprogramming empowers live-cell drug delivery: Mechanistic insights, delivery strategies, and clinical perspectives.Acta pharmaceutica Sinica. B · 2026Review
- Targeting Lysosomes for Enhanced Anti-Cancer Therapeutics and Immune Response.International journal of biological sciences · 2026Review
- Targeting Folate Receptors for the Detection and Selective Treatment of Cancer: Advanced Precision Oncology in Practice.International journal of biological sciences · 2026Review
- Metformin sensitizes non-small cell lung cancer to CDK4/6 inhibitor treatment by reducing lysosomal trapping.Science China. Life sciences · 2026Article
- HMGB1 downregulates DDX3 to activate the MAPK pathway, promoting the progression of colorectal cancer.Cancer gene therapy · 2025Article
- Tissue macrophages: origin, heterogenity, biological functions, diseases and therapeutic targets.Signal transduction and targeted therapy · 2025Review
- Urine proteomics-based analysis identifies CHI3L1 as an immune marker and potential therapeutic target for bladder cancer.BMC cancer · 2025Article
- Molecular Subtyping of Hepatocellular Carcinoma via Lysosome-Related Genes for Prognosis and Therapy Prediction.International journal of general medicine · 2025Article
- The multifaceted roles of cathepsins in immune and inflammatory responses: implications for cancer therapy, autoimmune diseases, and infectious diseases.Biomarker research · 2024Review
- A lysosome-targeted fluorescent probe for thiol detection in drug analysis and multiple biological systems.Analytical and bioanalytical chemistry · 2024Article
- Palbociclib-derived multifunctional molecules for lysosomal targeting and diagnostic-therapeutic integration.Future medicinal chemistry · 2024Article
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Authors and funding
15 authors at 4 institutions in 2 countries.
Funding
Abstract
backgroundPlatinum-drugs based chemotherapy in clinic increases the potency of tumor cells to produce M2 macrophages, thus leading to poor anti-metastatic activity and immunosuppression. Lysosome metabolism is critical for cancer cell migration and invasion, but how it promotes antitumor immunity in tumours and macrophages is poorly understood and the underlying mechanisms are elusive. The present study aimed to explore a synergistic strategy to dismantle the immunosuppressive microenvironment of tumours and metallodrugs discovery by using the herent metabolic plasticity.
methodsNaphplatin was prepared by coordinating an active alkaline moiety to cisplatin, which can regulate the lysosomal functions. Colorectal carcinoma cells were selected to perform the in vivo biological assays. Blood, tumour and spleen tissues were collected and analyzed by flow cytometry to further explore the relationship between anti-tumour activity and immune cells. Transformations of bone marrow derived macrophage (BMDM) and M2-BMDM to the M1 phenotype was confirmed after treatment with naphplatin. The key mechanisms of lysosome-mediated mucolipin-1(Mcoln1) and mitogen-activated protein kinase (MAPK) activation in M2 macrophage polarization have been unveiled. RNA sequencing (RNA-seq) was used to further explore the key mechanism underlying high-mobility group box 1(HMGB1)-mediated Cathepsin L(CTSL)-lysosome function blockade.
resultsWe demonstrated that naphplatin induces divergent lysosomal metabolic programs and reprograms macrophages in tumor cells to terminate the vicious tumour-associated macrophages (TAMs)-MDSCs-Treg triangle. Mechanistically, macrophages treated with naphplatin cause lysosome metabolic activation by triggering Ca
conclusionsThis study reveals the crucial strategies of macrophage-based metallodrugs discovery that are able to treat both immunologically "hot" and "cold" cancers. Different from traditional platinum-based antitumour drugs by inhibition of DNAs, we also deliver a strong antitumour strategy by targeting lysosome to induce divergent metabolic programs in macrophages and tumours for cancer immunotherapy.
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