Igniting cold tumors of intrahepatic cholangiocarcinoma: An insight into immune evasion and tumor immune microenvironment
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GRAPHICAL ABSTRACT
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PUBLIC SUMMARY
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Most intrahepatic cholangiocarcinomas (ICCs) present as cold tumors.
Immune evasion contributes to the cold phenotype of ICCs.
Cold ICCs are associated with an immunosuppressive tumor immune microenvironment.
Igniting cold ICCs can potentiate the efficacy of immunotherapy.
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ABSTRACT
Intrahepatic cholangiocarcinoma (ICC) is a rare hepatobiliary cancer that originates from the epithelium of the intrahepatic bile duct. The various treatments for ICC, such as chemotherapy, radiotherapy, and locoregional therapy, confer only modest improvements in survival rates. Immunotherapy, although revolutionary in cancer treatment, has found limited application in the treatment of ICCs due to the “cold” nature of these tumors, which is marked by scant T-cell infiltration. This characteristic makes immune checkpoint inhibitors (ICIs) unsuitable for the majority of ICC patients. Therefore, comprehensively understanding the mechanisms underlying these “cold” tumors is crucial for harnessing the potential of immunotherapy for treating ICC patients. This paper explores immune evasion mechanisms and the complex tumor immune microenvironment of ICC. This study provides a comprehensive overview of therapeutic strategies aimed at activating cold tumors and enhancing their immunogenicity. Furthermore, potential and promising targets for cancer vaccines and adoptive cellular therapy in the context of ICC are discussed. This endeavor strives to reveal new pathways for innovative immunotherapy strategies, with a focus on overcoming the key challenge of triggering an effective immune response in ICC patients. -
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REFERENCES
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Zhou X., Zhang B., Hu J., et al., (2024). Igniting cold tumors of intrahepatic cholangiocarcinoma: An insight into immune evasion and tumor immune microenvironment. The Innovation Medicine 2(1): 100052. https://doi.org/10.59717/j.xinn-med.2024.100052
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Zhou X., Zhang B., Hu J., et al., (2024). Igniting cold tumors of intrahepatic cholangiocarcinoma: An insight into immune evasion and tumor immune microenvironment. The Innovation Medicine 2(1): 100052. https://doi.org/10.59717/j.xinn-med.2024.100052
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Figure 1.
Characteristics of the three immunophenotypes of ICC
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Figure 2.
Mechanisms of immune evasion in cold ICCs
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Figure 3.
Origin, recruitment and phenotypic alteration of cellular components in ICC
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Figure 4.
Tumor immune microenvironment of ICC
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Figure 5.
Summary of the therapeutic strategies used to treat cold ICCs.
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Figure 6.
Therapeutic strategies targeting cellular components
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Figure 7.
Potential targets and biomarkers of novel immunotherapies for ICC
