Oxidized Low-Density Lipoprotein as a Potential Target for Enhancing Immune Checkpoint Inhibitor Therapy in Microsatellite-Stable Colorectal Cancer
Oxidized low-density lipoprotein (oxLDL) exhibits differential expression in microsatellite-stable (MSS) and microsatellite instability-high (MSI) colorectal cancer (CRC), highlighting its potential therapeutic role in immune checkpoint inhibitor (ICI) resistance in MSS CRC. Elevated oxLDL levels in...
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MDPI AG
2025-06-01
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| Series: | Antioxidants |
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| Online Access: | https://www.mdpi.com/2076-3921/14/6/726 |
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| author | Xiaochun Zhang Xiaorui Ye Heiying Jin |
| author_facet | Xiaochun Zhang Xiaorui Ye Heiying Jin |
| author_sort | Xiaochun Zhang |
| collection | DOAJ |
| description | Oxidized low-density lipoprotein (oxLDL) exhibits differential expression in microsatellite-stable (MSS) and microsatellite instability-high (MSI) colorectal cancer (CRC), highlighting its potential therapeutic role in immune checkpoint inhibitor (ICI) resistance in MSS CRC. Elevated oxLDL levels in MSS CRC contribute to tumor progression and diminish ICI efficacy by modulating metabolic reprogramming and immunosuppressive mechanisms within the tumor microenvironment (TME) by activating receptors such as LOX-1 and CD36. oxLDL triggers signaling pathways, including NF-κB, PI3K/Akt, and MAPK, leading to the expansion of immunosuppressive cells like regulatory T cells (Tregs), myeloid-derived suppressor cells (MDSCs), and M2 macrophages, while concurrently suppressing effector T cell functions. Additionally, oxLDL enhances oxidative stress and promotes fatty acid oxidation (FAO) and glycolytic metabolism, resulting in nutrient competition within the TME and establishing an immunosuppressive milieu, ultimately culminating in ICI resistance. This review systematically examines the disparities in oxLDL expression between MSS and MSI CRC and elucidates the molecular mechanisms through which oxLDL mediates ICI resistance. Furthermore, it explores potential therapeutic strategies targeting oxLDL, offering novel avenues to overcome immunotherapy resistance in MSS CRC. |
| format | Article |
| id | doaj-art-cc6cfcb02b40475a99eb4b6e128e69f9 |
| institution | Kabale University |
| issn | 2076-3921 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Antioxidants |
| spelling | doaj-art-cc6cfcb02b40475a99eb4b6e128e69f92025-08-20T03:27:11ZengMDPI AGAntioxidants2076-39212025-06-0114672610.3390/antiox14060726Oxidized Low-Density Lipoprotein as a Potential Target for Enhancing Immune Checkpoint Inhibitor Therapy in Microsatellite-Stable Colorectal CancerXiaochun Zhang0Xiaorui Ye1Heiying Jin2The Second Clinical Medical College of Nanjing University of Chinese Medicine, Nanjing 210017, ChinaThe Second Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing 210017, ChinaThe Second Clinical Medical College of Nanjing University of Chinese Medicine, Nanjing 210017, ChinaOxidized low-density lipoprotein (oxLDL) exhibits differential expression in microsatellite-stable (MSS) and microsatellite instability-high (MSI) colorectal cancer (CRC), highlighting its potential therapeutic role in immune checkpoint inhibitor (ICI) resistance in MSS CRC. Elevated oxLDL levels in MSS CRC contribute to tumor progression and diminish ICI efficacy by modulating metabolic reprogramming and immunosuppressive mechanisms within the tumor microenvironment (TME) by activating receptors such as LOX-1 and CD36. oxLDL triggers signaling pathways, including NF-κB, PI3K/Akt, and MAPK, leading to the expansion of immunosuppressive cells like regulatory T cells (Tregs), myeloid-derived suppressor cells (MDSCs), and M2 macrophages, while concurrently suppressing effector T cell functions. Additionally, oxLDL enhances oxidative stress and promotes fatty acid oxidation (FAO) and glycolytic metabolism, resulting in nutrient competition within the TME and establishing an immunosuppressive milieu, ultimately culminating in ICI resistance. This review systematically examines the disparities in oxLDL expression between MSS and MSI CRC and elucidates the molecular mechanisms through which oxLDL mediates ICI resistance. Furthermore, it explores potential therapeutic strategies targeting oxLDL, offering novel avenues to overcome immunotherapy resistance in MSS CRC.https://www.mdpi.com/2076-3921/14/6/726oxidized low-density lipoproteinmicrosatellite-stable colorectal cancerimmune checkpoint inhibitorstumor microenvironmentmetabolic reprogrammingimmunosuppression |
| spellingShingle | Xiaochun Zhang Xiaorui Ye Heiying Jin Oxidized Low-Density Lipoprotein as a Potential Target for Enhancing Immune Checkpoint Inhibitor Therapy in Microsatellite-Stable Colorectal Cancer Antioxidants oxidized low-density lipoprotein microsatellite-stable colorectal cancer immune checkpoint inhibitors tumor microenvironment metabolic reprogramming immunosuppression |
| title | Oxidized Low-Density Lipoprotein as a Potential Target for Enhancing Immune Checkpoint Inhibitor Therapy in Microsatellite-Stable Colorectal Cancer |
| title_full | Oxidized Low-Density Lipoprotein as a Potential Target for Enhancing Immune Checkpoint Inhibitor Therapy in Microsatellite-Stable Colorectal Cancer |
| title_fullStr | Oxidized Low-Density Lipoprotein as a Potential Target for Enhancing Immune Checkpoint Inhibitor Therapy in Microsatellite-Stable Colorectal Cancer |
| title_full_unstemmed | Oxidized Low-Density Lipoprotein as a Potential Target for Enhancing Immune Checkpoint Inhibitor Therapy in Microsatellite-Stable Colorectal Cancer |
| title_short | Oxidized Low-Density Lipoprotein as a Potential Target for Enhancing Immune Checkpoint Inhibitor Therapy in Microsatellite-Stable Colorectal Cancer |
| title_sort | oxidized low density lipoprotein as a potential target for enhancing immune checkpoint inhibitor therapy in microsatellite stable colorectal cancer |
| topic | oxidized low-density lipoprotein microsatellite-stable colorectal cancer immune checkpoint inhibitors tumor microenvironment metabolic reprogramming immunosuppression |
| url | https://www.mdpi.com/2076-3921/14/6/726 |
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