ArticleCancers2022
Midostaurin Modulates Tumor Microenvironment and Enhances Efficacy of Anti-PD-1 against Colon Cancer.
Article in Cancers, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 20 citations in OpenAlex.
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- THBS3 Functions as a Novel Biomarker for Prognosis and Immunotherapeutic Response in Colorectal Cancer: An Integrative Analysis and Validation of the Thrombospondin Gene Family.Cancer informatics · 2026Article
- Identification and validation of T cell senescence-related prognostic genes in gastric carcinoma and investigation of their potential regulatory mechanisms.Discover oncology · 2025Article
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- Characterization of mitochondrial metabolism related molecular subtypes and immune infiltration in colorectal adenocarcinoma.Scientific reports · 2024Article
- JAML inhibits colorectal carcinogenesis by modulating the tumor immune microenvironment.In vitro cellular & developmental biology. Animal · 2024Article
- The stimulator of interferon genes (STING) agonists for treating acute myeloid leukemia (AML): current knowledge and future outlook.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2023Review
- The combined signatures of the tumour microenvironment and nucleotide metabolism-related genes provide a prognostic and therapeutic biomarker for gastric cancer.Scientific reports · 2023Article
- TREX1 cytosolic DNA degradation correlates with autoimmune disease and cancer immunity.Clinical and experimental immunology · 2023Article
- Current trends and future prospects of drug repositioning in gastrointestinal oncology.Frontiers in pharmacology · 2023Review
- A novel signature of cuproptosis-related lncRNAs predicts prognosis in glioma: Evidence from bioinformatic analysis and experiments.Frontiers in pharmacology · 2023Article
- The role of ARL4C in predicting prognosis and immunotherapy drug susceptibility in pan-cancer analysis.Frontiers in pharmacology · 2023Article
- cGAS-STING signaling pathway in intestinal homeostasis and diseases.Frontiers in immunology · 2023Review
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
Abstract
Immunotherapy modulating the tumor microenvironment (TME) immune function has a promising effect on various types of cancers, but it remains as a limited efficacy in colon cancer. Midostaurin (PKC412) has been used in the clinical treatment of fms-like tyrosine kinase 3 (FLT3)-mutant acute myeloid leukemia and has demonstrated immunomodulatory activity. We aimed to evaluate the effect of midostaurin on the modulation of TME and the efficacy of anti-programmed cell death protein 1 (PD-1) against colon cancer. Midostaurin inhibited the growth of murine CT26 and human HCT116 and SW480 cells with multinucleation and micronuclei formation in morphology examination. The cell cycle arrested in the G2/M phase and the formation of the polyploid phase was noted. The formation of cytosolic DNA, including double-strand and single-strand DNA, was increased. Midostaurin increased mRNA expressions of cGAS, IRF3, and IFNAR1 in colorectal adenocarcinoma cells and mouse spleen macrophages. The protein expressions of Trex-1, c-KIT, and Flt3, but not PKCα/β/γ and VEGFR1, were down-regulated in midostaurin-treated colorectal adenocarcinoma cells and macrophages. Trex-1 protein expression was abrogated after FLT3L activation. In vivo, the combination of midostaurin and anti-PD-1 exhibited the greatest growth inhibition on a CT26-implanted tumor without major toxicity. TME analysis demonstrated that midostaurin alone decreased Treg cells and increased neutrophils and inflammatory monocytes. NKG2D
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