ArticleThe Journal of experimental medicine2022
CCR2/CCR5 inhibitor permits the radiation-induced effector T cell infiltration in pancreatic adenocarcinoma.
Article in The Journal of experimental medicine, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 54 papers, 2 of them syntheses that pooled it.
What it found
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
54 citing papers in PubMed, 2 syntheses or guidelines pooled it, 60 citations in OpenAlex.
- Mapping research trends in macrophage polarization and immunotherapeutic potential in prostate cancer: a bibliometric and visual analysis.Frontiers in oncology · 2026Pooled it
- Prognostic value of the neutrophil-to-lymphocyte ratio in patients with colorectal cancer undergoing chemotherapy: a systematic review and meta-analysis.Frontiers in oncology · 2026Pooled it
- CCR5 as a Therapeutic Target in HIV Disease: From CRISPR/Cas9 Gene Editing to Maraviroc-Mediated Inhibition.Viruses · 2026Review
- Challenges and opportunities in combining radiotherapy and immunotherapy for localized pancreatic cancer.Nature reviews. Gastroenterology & hepatology · 2026Review
- Targeting CCR1 Remodels the Tumor Microenvironment and Relieves Immunosuppression in Pancreatic Cancer.Cancer immunology research · 2026Article
- CCL5 improves radiation resistance through activation of the AMPK/mTOR pathway in adenoid cystic carcinoma.Journal of translational medicine · 2026Article
- The Double-Edged Sword: How Radiotherapy Shapes the Tumor Immune Microenvironment to Modulate Responses to Checkpoint Inhibitors.International journal of molecular sciences · 2026Review
- CXCR2 blockade overcomes the NETosis-mediated resistance to MEK inhibition in pancreatic cancer models.The Journal of clinical investigation · 2026Article
- Spatiotemporal dynamics of radioresistance: decoding macrophage-driven radioprotective niches through temporal-spatial reprogramming.Molecular cancer · 2026Review
- CCR2-driven monocyte recruitment is protective against radiotherapy-induced intestinal toxicity.Mucosal immunology · 2026Article
- Role of tumor microenvironment in regulator of tumor progression and immunotherapy.Discover oncology · 2026Review
- Targeting Tumor-Associated Macrophages to Reshape the Immuno-Mechanical Landscape: Molecular Mechanisms and Therapeutic Strategies.International journal of biological sciences · 2026Review
- CCR-CCL axes as key upstream influencers of pancreatic ductal adenocarcinoma: CCR2-CCL2, CCR5-CCL5, CCR4-CCL17/22, CCR6-CCL20, CCR7-CCL19/21.Frontiers in immunology · 2026Review
- The chemokine network in lupus nephritis: pathogenesis, targeted therapies, and future directions.Frontiers in pharmacology · 2026Review
- Innate immunity-stroma crosstalk in pancreatic cancer: overcoming spatial and metabolic barriers to immunotherapy.Frontiers in immunology · 2026Review
- The tumour microenvironment in pancreatic cancer - new clinical challenges, but more opportunities.Nature reviews. Clinical oncology · 2025Review
- Neutrophil Extracellular Traps Modulate Recruitment and Immunosuppression of Macrophages in Pancreatic Adenocarcinoma.Cancer immunology research · 2025Article
- Killing the killers: Natural killer cell therapy targeting glioma stem cells in high-grade glioma.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Review
- Article
- Distinct response to IL-1β blockade in liver- and lung-specific metastasis mouse models of pancreatic cancer with heterogeneous tumor microenvironments.Experimental hematology & oncology · 2025Article
Corrections and comments
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Authors and funding
22 authors at 3 institutions in 1 country.
Funding
Abstract
The resistance of pancreatic ductal adenocarcinoma (PDAC) to immune checkpoint inhibitors (ICIs) is attributed to the immune-quiescent and -suppressive tumor microenvironment (TME). We recently found that CCR2 and CCR5 were induced in PDAC following treatment with anti-PD-1 antibody (αPD-1); thus, we examined PDAC vaccine or radiation therapy (RT) as T cell priming mechanisms together with BMS-687681, a dual antagonist of CCR2 and CCR5 (CCR2/5i), in combination with αPD-1 as new treatment strategies. Using PDAC mouse models, we demonstrated that RT followed by αPD-1 and prolonged treatment with CCR2/5i conferred better antitumor efficacy than other combination treatments tested. The combination of RT + αPD-1 + CCR2/5i enhanced intratumoral effector and memory T cell infiltration but suppressed regulatory T cell, M2-like tumor-associated macrophage, and myeloid-derived suppressive cell infiltration. RNA sequencing showed that CCR2/5i partially inhibited RT-induced TLR2/4 and RAGE signaling, leading to decreased expression of immunosuppressive cytokines including CCL2/CCL5, but increased expression of effector T cell chemokines such as CCL17/CCL22. This study thus supports the clinical development of CCR2/5i in combination with RT and ICIs for PDAC treatment.
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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.