ArticleJournal for immunotherapy of cancer2021
Combined inhibition of CXCL12 and PD-1 in MSS colorectal and pancreatic cancer: modulation of the microenvironment and clinical effects.
Article in Journal for immunotherapy of cancer, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 58 papers, 4 of them syntheses that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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
58 citing papers in PubMed, 4 syntheses or guidelines pooled it, 73 citations in OpenAlex.
- Signaling pathway mechanisms in pancreatic ductal adenocarcinoma tumor microenvironment and emerging targeting strategies for improved prognosis.Oncology reviews · 2026Pooled it
- Global hotspots and trends in pre-metastatic niche research: a bibliometric analysis(2005-2024).Frontiers in immunology · 2025Pooled it
- Chemokines as Prognostic Factor in Colorectal Cancer Patients: A Systematic Review and Meta-Analysis.International journal of molecular sciences · 2024Pooled it
- The Efficacy of Immune Checkpoint Inhibitors in Microsatellite Stable Colorectal Cancer: A Systematic Review.The oncologist · 2024Pooled it
- CD8⁺ T Cell infiltration and spatial organization in cancer: mechanisms, barriers, and therapeutic strategies.Molecular biomedicine · 2026Review
- Targeting cancer-associated fibroblasts: therapeutic strategies, translational challenges, and future perspectives.Journal of hematology & oncology · 2026Review
- Machine learning-driven M2 macrophage signature for precision prediction of survival and therapy response in acute myeloid leukemia.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2026Article
- Cancer-associated fibroblast targeting therapies as a tool to enhance responses to radiotherapy and immunotherapy.Journal for immunotherapy of cancer · 2026Review
- Mechanisms of Resistance and Synergy: The Role of Tumor Microenvironment in HER2-Low Breast Cancer Therapy.Pharmaceuticals (Basel, Switzerland) · 2026Review
- Integrated single-cell and spatial transcriptomic analysis reveals mCAF-SPP1⁺ macrophage-T cell crosstalk shaping immunosuppressive niches in colorectal cancer liver metastasis.Journal of translational medicine · 2026Article
- Peritumoural adipose tissue drives immune evasion in colorectal cancer via adipose-mesenchymal transformation.Nature cell biology · 2026Article
- A review of the current evidence for maintenance therapy in gastric cancer.Frontiers in pharmacology · 2026Review
- Targeting FAP/CAFs to rewire immune-excluded and resistant tumor niches.Frontiers in pharmacology · 2026Review
- Cancer-associated fibroblasts in the lung cancer microenvironment from multi-dimensional mechanisms to therapeutic strategies.Frontiers in oncology · 2026Review
- Targeting neutrophil-driven immunosuppression: A strategy to overcome immune checkpoint inhibitor resistance.Clinical and translational medicine · 2026Review
- Cancer-associated fibroblasts in the tumor microenvironment: heterogeneity, crosstalk mechanisms, and therapeutic implications.Molecular cancer · 2025Review
- Harnessing the power of cancer-associated fibroblasts to revolutionize pancreatic cancer treatment.Cancer biology & medicine · 2025Review
- Arteriolar angiogenesis: implications in anti-angiogenic immunotherapy for pancreatic cancers.Cytokine & growth factor reviews · 2025Review
- A pan-cancer single-cell analysis reveals the effect of PD-1 blockades on tumor angiogenesis by inhibiting the endothelial CXCL12-CXCR4 axis.Cancer immunology, immunotherapy : CII · 2025Article
- Cancer-associated fibroblast-derived circKLHL24 drives perineural invasion in pancreatic cancer via dual regulation of the sec31a-CXCL12 axis.Journal of experimental & clinical cancer research : CR · 2025Article
Corrections and comments
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Authors and funding
14 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundImmunotherapy in microsatellite stable colorectal or pancreatic cancer has not shown promising results. It has been hypothesized that targeting immunosuppressive molecules like SDF1-alpha/CXCL12 could contribute to immunotherapy and animal models showed promising results on T cell activation and migration in combination with immune checkpoint inhibition.
methodsHere, we describe the successful application of anti-CXCL12 (NOX-A12) in patients with advanced stage pretreated metastatic colorectal and pancreatic cancer (OPERA trial). The treatment consisted of 2 weeks of anti-CXCL12 monotherapy with NOX-A12 followed by combination therapy with pembrolizumab (n=20 patients) until progression or intolerable toxicity had occurred.
resultsThe treatment was safe and well tolerated with 83.8% grade I/II, 15.5% grade III and 0.7% grade V adverse events. Of note, for a majority of patients, time on trial treatment was prolonged compared with their last standard treatment preceding trial participation. Systematic serial biopsies revealed distinct patterns of modulation. Tissue and clinical responses were associated with Th1-like tissue reactivity upon CXCL12 inhibition. A downregulation of a cytokine cassette of interleukin (IL)-2/IL-16/CXCL-10 was associated with tumor resistance and furthermore linked to a rare, CXCL12-associated CD14
conclusionsWe demonstrate that the combination of CXCL12 inhibition and checkpoint inhibition is safe and grants further exploration of synergistic combinatorial strategies.
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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.