ArticleGut2025
Induction of macrophage efferocytosis in pancreatic cancer via PI3Kγ inhibition and radiotherapy promotes tumour control.
Article in Gut, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed.
- Glioma microenvironment: Cellular crosstalk, immunosuppression, and novel therapeutic perspectives.Chinese medical journal · 2026Review
- Spatial and Temporal Heterogeneity of Macrophage Efferocytosis in Tumors: Emerging Implications for Immunotherapy Biomarkers and Therapeutic Timing.Cancer medicine · 2026Review
- RAS signaling at the crossroads of radioresistance and tumor immunity.Journal for immunotherapy of cancer · 2026Review
- Integrin-mediated mechanotransduction in the tumor microenvironment: macrophage-centered signaling mechanisms and immune remodeling.Journal of translational medicine · 2026Review
- Fungal metabolite-based immunotherapy overcomes tumor-associated macrophage immunosuppression.Cell reports. Medicine · 2026Article
- Spatiotemporal dynamics of radioresistance: decoding macrophage-driven radioprotective niches through temporal-spatial reprogramming.Molecular cancer · 2026Review
- The central role of radiotherapy in remodeling the tumor immune microenvironment: mechanisms and therapeutic implications.Frontiers in cell and developmental biology · 2026Review
- Radiotherapy-synergized in situ hydrogel vaccine with engineeredFrontiers in immunology · 2026Article
- Tumor-associated macrophages: potential therapeutic strategies and future prospects in radioresistance of cancer.Frontiers in immunology · 2026Review
- Tumor-Derived Interleukin 35 Promotes Fibrosis in the Tumor Microenvironment of Pancreatic Cancer by Activating Pancreatic Stellate Cells.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Targeting Tumor-Associated Macrophages to Reshape the Immuno-Mechanical Landscape: Molecular Mechanisms and Therapeutic Strategies.International journal of biological sciences · 2026Review
- Comprehensive analysis of fatty acid desaturase 3 in clear cell renal cell carcinoma: insights into tumor progression, immune microenvironment, and clinical outcomes.Frontiers in immunology · 2026Article
- Integrated bulk and single-cell transcriptomics to develop an efferocytosis-related prognostic model for lung adenocarcinoma and validate the key gene LDHA.European journal of medical research · 2025Article
- The Role of PI3K/AKT/mTOR Signaling in Tumor Radioresistance and Advances in Inhibitor Research.International journal of molecular sciences · 2025Review
- Roles of immunosuppressive myeloid states in colorectal cancer checkpoint inhibitor non-response: single-cell and spatial proteomics, and reprogramming approaches.Frontiers in immunology · 2025Review
- Macrophage polarization: molecular mechanisms, disease implications, and targeted therapeutic strategies.Frontiers in immunology · 2025Review
- Immunosuppressive tumor microenvironment in pancreatic cancer: mechanisms and therapeutic targets.Frontiers in immunology · 2025Review
Corrections and comments
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Authors and funding
14 authors.
Funding
Abstract
backgroundThe immune suppression mechanisms in pancreatic ductal adenocarcinoma (PDAC) remain unknown, but preclinical studies have implicated macrophage-mediated immune tolerance. Hence, pathways that regulate macrophage phenotype are of strategic interest, with reprogramming strategies focusing on inhibitors of phosphoinositide 3-kinase-gamma (PI3Kγ) due to restricted immune cell expression. Inhibition of PI3Kγ alone is ineffective in PDAC, despite increased infiltration of CD8+ T cells.
objectiveWe hypothesised that the immune stimulatory effects of radiation, and its ability to boost tumour antigen availability could synergise with PI3Kγ inhibition to augment antitumour immunity.
designWe used orthoptic and genetically engineered mouse models of pancreatic cancer (LSL-Kras
resultsTumour-associated macrophages that employ efferocytosis to eradicate apoptotic cells can be redirected to present tumour antigens, stimulate CD8+ T cell responses and increase local tumour control. Specifically, we demonstrate how PI3Kγ signalling restricts inflammatory macrophages and that inhibition supports MERTK-dependent efferocytosis. We further find that the combination of PI3Kγ inhibition with targeted radiotherapy stimulates inflammatory macrophages to invoke a pathogen-induced like efferocytosis that switches from immune tolerant to antigen presenting.
conclusionsOur data supports a new immunotherapeutic approach and a translational rationale to improve survival in PDAC.
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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.