ArticleCancer research2022
PIM2 Expression Induced by Proinflammatory Macrophages Suppresses Immunotherapy Efficacy in Hepatocellular Carcinoma.
Article in Cancer research, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 24 citations in OpenAlex.
- Identification of Autophagy-related Genes of the Osteoarthritis Using Machine Learning Algorithm.Biochemical genetics · 2026Article
- CD47-mediated efferocytosis in diseases: A comprehensive review.Molecular biology reports · 2026Review
- Tissue-Resident Macrophage in Inflammation and Cancer.MedComm · 2026Review
- Tescalcin is a phagocytic checkpoint driving immune escape and limiting immunotherapeutic efficacy in hepatocellular carcinoma.The Journal of clinical investigation · 2026Article
- Therapy-induced remodeling of the tumor immune microenvironment: Mechanistic insights and implications for immunotherapy.Chinese medical journal · 2026Review
- CCL25/CCR9-induced M2 macrophage polarization promotes lung cancer progression via TGF-β1-mediated activation of the JAK/STAT-PIM2 signaling pathway.Molecular and cellular biochemistry · 2026Article
- Targeting SPAK suppresses progression and averts an immune exhaustive microenvironment in hepatocellular carcinoma.Nature communications · 2026Article
- The cost of persistent alarm: temporal transcriptional reprogramming of macrophages from acute activation to chronic immune suppression by day 11.Frontiers in immunology · 2026Article
- Molecular innate immune programs of tumor-associated macrophages in immune checkpoint blockade resistance: a staged framework from suppressive circuitry to translational bottlenecks.Frontiers in immunology · 2026Review
- Mechanisms of Immune Checkpoint Inhibitor Resistance in Hepatocellular Carcinoma and Strategies for Reversal.Cancers · 2025Review
- Inhibition of PIM Kinase in Tumor-Associated Macrophages Suppresses Inflammasome Activation and Sensitizes Prostate Cancer to Immunotherapy.Cancer immunology research · 2025Article
- Modified Xi-Jiao-Di-Huang Decoction Alleviates Sepsis via Regulating Macrophage Polarization by Inhibiting the PIM2/NF-κB Pathway.Journal of inflammation research · 2025Article
- A novel glycolysis-related gene signature for predicting prognosis and immunotherapy efficacy in breast cancer.Frontiers in immunology · 2025Article
- ZDHHC5 as a central regulator in a palmitoylation-associated prognostic model for lung adenocarcinoma: insights from pan-cancer and experimental analyses.Frontiers in immunology · 2025Article
- YTHDF2 in peritumoral hepatocytes mediates chemotherapy-induced antitumor immune responses through CX3CL1-mediated CD8Molecular cancer · 2024Article
- NF-κB in biology and targeted therapy: new insights and translational implications.Signal transduction and targeted therapy · 2024Review
- A novel signature based on twelve programmed cell death patterns to predict the prognosis of lung adenocarcinoma.American journal of translational research · 2024Article
- Regulation of cagA-Helicobacter on gastric PIM2 expression in gastric cancer.Cancer biomarkers : section A of Disease markers · 2024Article
- Review
- Dihydroquercetin/Taxifolin Inhibits METTL3/mKidney diseases (Basel, Switzerland)Article
Corrections and comments
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Authors and funding
16 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Cancer immunotherapy restores or enhances the effector function of T cells in the tumor microenvironment, but the efficacy of immunotherapy has been hindered by therapeutic resistance. Here, we identify the proto-oncogene serine/threonine protein kinase PIM2 as a novel negative feedback regulator of IFNγ-elicited tumor inflammation, thus endowing cancer cells with aggressive features. Mechanistically, IL1β derived from IFNγ-polarized tumor macrophages triggered PIM2 expression in cancer cells via the p38 MAPK/Erk and NF-κB signaling pathways. PIM2+ cancer cells generated by proinflammatory macrophages acquired the capability to survive, metastasize, and resist T-cell cytotoxicity and immunotherapy. A therapeutic strategy combining immune checkpoint blockade (ICB) with IL1β blockade or PIM2 kinase inhibition in vivo effectively and successfully elicited tumor regression. These results provide insight into the regulatory and functional features of PIM2+ tumors and suggest that strategies to influence the functional activities of inflammatory cells or PIM2 kinase may improve the efficacy of immunotherapy. SIGNIFICANCE: Cross-talk between T cells and macrophages regulates cancer cell PIM2 expression to promote cancer aggressiveness, revealing translational approaches to improve response to ICB in hepatocellular carcinoma.
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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.