ArticleCancer research2023
FGFR3 Alterations in Bladder Cancer Stimulate Serine Synthesis to Induce Immune-Inert Macrophages That Suppress T-cell Recruitment and Activation.
Article in Cancer research, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers, 1 of them a synthesis that pooled it.
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Who cites it
42 citing papers in PubMed, 1 synthesis or guideline pooled it, 38 citations in OpenAlex.
- Hyperprogressive disease in carcinoma induced by immune checkpoint inhibitor therapy: a systematic review.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2026Pooled it
- pH-responsive biomimetic liposomes enhance targeted immunotherapy of bladder cancer.Science China. Life sciences · 2026Article
- FGF18 mediates fibroblast-leukemia cross talk to promote acute myeloid leukemia progression.Blood · 2026Article
- CHD6 promotes triple-negative breast cancer progression and is associated with PI3K/AKT and MAPK pathways.International journal of clinical oncology · 2026Article
- Heterogeneity of urinary system tumors: novel avenues for targeted therapy and precision medicine.Journal of advanced research · 2026Review
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- Article
- The ZIF-8 nanoplatform targeted delivery of IFI44 siRNA to suppress bladder cancer development via modulating the PI3K/AKT signaling pathway.Journal of nanobiotechnology · 2026Article
- Multi-omics integration constructs a senescence-based prognostic model and identifies EIF4EBP1 as a therapeutic target in clear cell renal cell carcinoma.Discover oncology · 2026Article
- LIS1 mediated Schwann cell reprogramming enhances perineural invasion by activating the serine/NMDAR/AKT signaling pathway in head and neck squamous carcinoma.Cancer cell international · 2026Article
- Post-translational modifications: Principal regulators of bladder cancer.Molecular biology reports · 2026Review
- Integrated Multi-Omics Profiling Identifies an Immunotherapy Vulnerable and Prognostic Associated Subtype in Cholangiocarcinoma.Liver cancer · 2026Article
- SREBP2-RAB11A-ZDHHC20 axis orchestrates FGFR3 palmitoylation and membrane retention to drive bladder cancer progression.Cellular oncology (Dordrecht, Netherlands) · 2026Article
- Article
- Unraveling the FGFR-RNA splicing axis: Mechanisms, oncogenic crosstalks and innovations for therapeutic purpose.Acta pharmaceutica Sinica. B · 2026Review
- Perspective on the integration of radiomics and spatial omics in the analysis of the tumor microenvironment of bladder cancer and prospects for precision diagnosis and treatment.Frontiers in immunology · 2026Review
- One-carbon metabolism in cancer immunity: T-cell fitness, epigenetic programming, and therapeutic opportunities.Frontiers in immunology · 2026Review
- The mechanism of PKM2/HIF-1α axis polarizing TAMs by upregulating glucose-serine metabolism to promote melanoma progression.Frontiers in immunology · 2026Article
- The "serine code" of metabolic reprogramming: multidimensional roles of the serine synthesis pathway in tumors and novel breakthroughs for targeted therapy.Frontiers in immunology · 2026Review
- FGFR signaling and apoptotic regulation in cancer: links to immune evasion, therapeutic resistance, and treatment re-engagement.Frontiers in immunology · 2026Review
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Authors and funding
13 authors at 3 institutions in 1 country.
Funding
Abstract
FGFR3 alterations are common in patients with bladder cancer. While the FGFR tyrosine kinase inhibitor erdafitinib has been approved as a targeted therapy for patients with FGFR3-altered (aFGFR3) bladder cancer, the response rate remains suboptimal, prompting development of strategies to improve treatment response. Here, we observed an immune-desert tumor microenvironment (TME) phenotype in human aFGFR3 bladder cancer and demonstrated that mutant FGFR3 indirectly induces a "cold" TME in mouse bladder cancer models. Single-cell RNA sequencing revealed the central role of macrophages in inducing the cold TME of aFGFR3 tumors. Macrophages in aFGFR3 tumors exhibited reduced T-cell recruitment and antigen presentation capabilities. Increased serine synthesis in bladder cancer cells that was induced by mutant FGFR3 activated the PI3K/Akt pathway in macrophages, shifting them to an immune-inert phenotype. Targeting PI3K in aFGFR3 tumors with duvelisib achieved promising efficacy by reversing the macrophage phenotype, and combination therapy with duvelisib and erdafitinib demonstrated increased antitumor activity. Overall, these findings reveal the critical role of enhanced serine synthesis efflux from cancer cells with mutant FGFR3 in shifting macrophages to an immune-inert phenotype. Reversing the macrophage phenotype holds promise for enhancing erdafitinib efficacy. SIGNIFICANCE: Metabolic reprogramming of bladder cancer cells driven by mutant FGFR3 increases serine synthesis that suppresses macrophage immunostimulatory functions to generate an immunosuppressive TME, which can be overcome by targeting PI3K.
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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.