ArticleCancer immunology research2022
Tumor-Derived Lactic Acid Modulates Activation and Metabolic Status of Draining Lymph Node Stroma.
Article in Cancer immunology research, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 36 citations in OpenAlex.
- Quantifying the Long and Short Axes of the External Iliac Lymph Nodes Using Dual-Energy Computed Tomography: A Potential Diagnostic Approach for Periprosthetic Joint Infection - A Prospective Study.Infection and drug resistance · 2024Trial
- Lymph node extracellular matrix skews the immune function of human fibroblastic reticular cells.iScience · 2026Article
- Targeting Lactate and Lactylation in Cancer Metabolism and Immunotherapy.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- Immune remodeling of tumor-draining lymph nodes: mechanistic determinants of checkpoint blockade responsiveness.Frontiers in immunology · 2026Review
- Immunometabolic Reprogramming of Fibroblastic Reticular Cells in the Tumor Immune Microenvironment.BioMed research international · 2026Review
- Adipocytes-induced ANGPTL4/KLF4 axis drives glycolysis and metastasis in triple-negative breast cancer.Journal of experimental & clinical cancer research : CR · 2025Article
- Emerging strategies in lymph node-targeted nano-delivery systems for tumor immunotherapy.Essays in biochemistry · 2025Review
- Molecular Underpinnings of Brain Metastases.International journal of molecular sciences · 2025Review
- Targeting glycolytic reprogramming by tsRNA-0032 for treating pathological lymphangiogenesis.Cell death & disease · 2025Article
- Modeling the lymph node stromal cells in oral squamous cell carcinoma: insights into the stromal cues in nodal metastasis.Human cell · 2025Article
- Asiaticoside-nitric oxide synergistically accelerate diabetic wound healing by regulating key metabolites and SRC/STAT3 signaling.Burns & trauma · 2025Article
- Pipelines for lymphocyte homeostasis maintenance during cancer immunotherapy.Frontiers in immunology · 2025Review
- Lymphoid stroma in all its states.Frontiers in immunology · 2025Review
- Metabolism and epigenetics in cancer: toward personalized treatment.Frontiers in endocrinology · 2025Review
- Reference gene evaluation for normalization of gene expression studies with lymph tissue and node‑derived stromal cells of patients with oral squamous cell carcinoma.Oncology letters · 2024Article
- Dendritic Cell-Hitchhiking In Vivo for Vaccine Delivery to Lymph Nodes.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Same yet different - how lymph node heterogeneity affects immune responses.Nature reviews. Immunology · 2024Review
- NAMPT-Driven M2 Polarization of Tumor-Associated Macrophages Leads to an Immunosuppressive Microenvironment in Colorectal Cancer.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Lymphatic system regulation of anti-cancer immunity and metastasis.Frontiers in immunology · 2024Review
- Protective fibroblastic niches in secondary lymphoid organs.The Journal of experimental medicine · 2024Review
Corrections and comments
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Authors and funding
16 authors at 5 institutions in 4 countries.
Funding
Abstract
Communication between tumors and the stroma of tumor-draining lymph nodes (TDLN) exists before metastasis arises, altering the structure and function of the TDLN niche. Transcriptional profiling of fibroblastic reticular cells (FRC), the dominant stromal population of lymph nodes, has revealed that FRCs in TDLNs are reprogrammed. However, the tumor-derived factors driving the changes in FRCs remain to be identified. Taking an unbiased approach, we have shown herein that lactic acid (LA), a metabolite released by cancer cells, was not only secreted by B16.F10 and 4T1 tumors in high amounts, but also that it was enriched in TDLNs. LA supported an upregulation of Podoplanin (Pdpn) and Thy1 and downregulation of IL7 in FRCs of TDLNs, making them akin to activated fibroblasts found at the primary tumor site. Furthermore, we found that tumor-derived LA altered mitochondrial function of FRCs in TDLNs. Thus, our results demonstrate a mechanism by which a tumor-derived metabolite connected with a low pH environment modulates the function of fibroblasts in TDLNs. How lymph node function is perturbed to support cancer metastases remains unclear. The authors show that tumor-derived LA drains to lymph nodes where it modulates the function of lymph node stromal cells, prior to metastatic colonization.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.