ArticleCancer immunology, immunotherapy : CII2025
IDO1 inhibitor enhances the effectiveness of PD-1 blockade in microsatellite stable colorectal cancer by promoting macrophage pro-inflammatory phenotype polarization.
Article in Cancer immunology, immunotherapy : CII, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers, 1 of them a synthesis that pooled it.
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Who cites it
25 citing papers in PubMed, 1 synthesis or guideline pooled it.
- The prognostic value of indoleamine 2,3-dioxygenase in colorectal cancer: a systematic review and meta-analysis.BMC gastroenterology · 2025Pooled it
- Phase 1 study of KHK2455, a long-acting, potent and selective IDO1 inhibitor, in combination with avelumab in patients with locally advanced or metastatic urothelial carcinoma.Journal for immunotherapy of cancer · 2026Article
- Compensatory pathways in tryptophan metabolism and immune regulation following IDO inhibition.Molecular biology reports · 2026Review
- Tryptophan metabolism in tumor microenvironment and therapeutic implications.Journal of advanced research · 2026Review
- Tryptophan metabolism in colorectal cancer: From mechanistic insights to novel therapeutic strategies.Clinical and translational medicine · 2026Review
- Review
- Enhancing Immunotherapeutic Response in Colorectal Cancer with a Neuropilin 1-Targeting Tumor-Penetrating Peptide.Cancer research communications · 2026Article
- Multi-omics integration identifies ribosome biogenesis-active macrophage subpopulation and its key gene GNL2 in driving liver hepatocellular carcinoma progression and mechanisms.Cancer cell international · 2026Article
- The Tryptophan Paradox: From Microbiome-Mediated Homeostasis to Tumor-Driven Immune Escape.International journal of molecular sciences · 2026Review
- Advancing Small-Molecule Immunotherapy Through Polymeric Micelle Delivery.Pharmaceutics · 2026Review
- Endogenous immune recruitment in glioblastoma CAR T therapy: cytokine, myeloid, and chemokine circuitry.Journal of neuro-oncology · 2026Review
- Metabolic reprogramming in cancer: signaling pathways and therapeutic targets.Molecular cancer · 2026Review
- Tumor microenvironment dynamics in gastric cancer pathogenesis and therapeutic resistance.Molecular cancer · 2026Review
- Bicaudal‑C1 in Cancer: Molecular Mechanisms and Therapeutic Strategies Integrating Chinese and Western Medicine.Drug design, development and therapy · 2026Review
- Metabolic reprogramming and immune evasion interaction in the tumor microenvironment promote tumor progression.Frontiers in oncology · 2026Review
- 3-hydroxyanthranilic acid suppresses colorectal cancer growth and enhances 5-fluorouracil sensitivity via the YY1-p53 and YY1-DKK4 axes.Frontiers in pharmacology · 2026Article
- Dual inhibition of CSF-1R and IDO modulates the fibrotic and immunosuppressive tumor microenvironment in pancreatic ductal adenocarcinoma.Frontiers in immunology · 2026Article
- Multicellular immunosuppressive networks in microsatellite-stable colorectal cancer: CD8+ T cell exclusion, dysfunction, exhaustion, and therapeutic implications.Frontiers in immunology · 2026Review
- Adaptive immunotherapeutic paradigms in diffuse midline glioma: integrating epigenetic reprogramming, neuron-glioma interactions, and tumor microenvironment modulation.Journal of neuro-oncology · 2025Review
- Modulation of the tumor microenvironment by the ubiquitin-proteasome system in colorectal cancer.Journal of translational medicine · 2025Review
Corrections and comments
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Authors and funding
8 authors.
Funding
Abstract
Microsatellite stable (MSS) colorectal cancer (CRC) is a subtype of CRC that generally exhibits resistance to immunotherapy, particularly immune checkpoint inhibitors such as PD-1 blockade. This study investigates the effects and underlying mechanisms of combining PD-1 blockade with IDO1 inhibition in MSS CRC. Bioinformatics analyses of TCGA-COAD and TCGA-READ cohorts revealed significantly elevated IDO1 expression in CRC tumors, correlating with tumor mutation burden across TCGA datasets. In vivo experiments demonstrated that the combination of IDO1 inhibition and PD-1 blockade significantly reduced tumor growth and increased immune cell infiltration, particularly pro-inflammatory macrophages and CD8+ T cells. IDO1 knockdown in CRC cell lines impaired tolerance to interferon-γ and increased apoptosis in vitro, which were rescued by the application of kynurenine, the end product of IDO1. IDO1 knockdown in MSS CRC enhanced the effectiveness of PD-1 blockade therapy in vivo. IDO1 knockdown cancer cells promoted pro-inflammatory macrophage polarization and enhanced phagocytic activity in vitro, associated with the upregulation of JAK2-STAT3-IL6 signaling pathway. These findings highlight the role of IDO1 in modulating the tumor immune microenvironment in MSS CRC and suggest that combining PD-1 blockade with IDO1 inhibition could enhance therapeutic efficacy by promoting macrophage pro-inflammatory polarization and infiltration through the JAK2-STAT3-IL6 pathway.
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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.