Microsatellite Instability and Immune Response: From Microenvironment Features to Therapeutic Actionability—Lessons from Colorectal Cancer
Microsatellite instability (MSI) can be found in 15–20% of all colorectal cancers (CRC) and is the key feature of a defective DNA mismatch repair (MMR) system. Currently, MSI has been established as a unique and pivotal biomarker in the diagnosis, prognosis, and treatment of CRC. MSI tumors display...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-05-01
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| Series: | Genes |
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| Online Access: | https://www.mdpi.com/2073-4425/14/6/1169 |
| _version_ | 1797594680192401408 |
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| author | Luana Greco Federica Rubbino Arianna Dal Buono Luigi Laghi |
| author_facet | Luana Greco Federica Rubbino Arianna Dal Buono Luigi Laghi |
| author_sort | Luana Greco |
| collection | DOAJ |
| description | Microsatellite instability (MSI) can be found in 15–20% of all colorectal cancers (CRC) and is the key feature of a defective DNA mismatch repair (MMR) system. Currently, MSI has been established as a unique and pivotal biomarker in the diagnosis, prognosis, and treatment of CRC. MSI tumors display a strong lymphocytic activation and a shift toward a tumoral microenvironment restraining metastatic potential and ensuing in a high responsiveness to immunotherapy of MSI CRC. Indeed, neoplastic cells with an MMR defect overexpress several immune checkpoint proteins, such as programmed death-1 (PD-1) and programmed death-ligand 1(PD-L1), that can be pharmacologically targeted, allowing for the revival the cytotoxic immune response toward the tumor. This review aims to illustrate the role of MSI in the tumor biology of colorectal cancer, focusing on the immune interactions with the microenvironment and their therapeutic implications. |
| first_indexed | 2024-03-11T02:25:43Z |
| format | Article |
| id | doaj.art-bf6504db8a54412b85b6553d33c1c007 |
| institution | Directory Open Access Journal |
| issn | 2073-4425 |
| language | English |
| last_indexed | 2024-03-11T02:25:43Z |
| publishDate | 2023-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Genes |
| spelling | doaj.art-bf6504db8a54412b85b6553d33c1c0072023-11-18T10:33:46ZengMDPI AGGenes2073-44252023-05-01146116910.3390/genes14061169Microsatellite Instability and Immune Response: From Microenvironment Features to Therapeutic Actionability—Lessons from Colorectal CancerLuana Greco0Federica Rubbino1Arianna Dal Buono2Luigi Laghi3Laboratory of Molecular Gastroenterology, IRCCS Humanitas Research Hospital, Via Manzoni 56, 20089 Rozzano, ItalyLaboratory of Molecular Gastroenterology, IRCCS Humanitas Research Hospital, Via Manzoni 56, 20089 Rozzano, ItalyDivision of Gastroenterology, Department of Gastroenterology, IRCCS Humanitas Research Hospital, Via Manzoni 56, 20089 Rozzano, ItalyLaboratory of Molecular Gastroenterology, IRCCS Humanitas Research Hospital, Via Manzoni 56, 20089 Rozzano, ItalyMicrosatellite instability (MSI) can be found in 15–20% of all colorectal cancers (CRC) and is the key feature of a defective DNA mismatch repair (MMR) system. Currently, MSI has been established as a unique and pivotal biomarker in the diagnosis, prognosis, and treatment of CRC. MSI tumors display a strong lymphocytic activation and a shift toward a tumoral microenvironment restraining metastatic potential and ensuing in a high responsiveness to immunotherapy of MSI CRC. Indeed, neoplastic cells with an MMR defect overexpress several immune checkpoint proteins, such as programmed death-1 (PD-1) and programmed death-ligand 1(PD-L1), that can be pharmacologically targeted, allowing for the revival the cytotoxic immune response toward the tumor. This review aims to illustrate the role of MSI in the tumor biology of colorectal cancer, focusing on the immune interactions with the microenvironment and their therapeutic implications.https://www.mdpi.com/2073-4425/14/6/1169microsatellite instabilityDNA mismatch repaircolorectal cancerhereditary syndromeimmunotherapymicroenviroment |
| spellingShingle | Luana Greco Federica Rubbino Arianna Dal Buono Luigi Laghi Microsatellite Instability and Immune Response: From Microenvironment Features to Therapeutic Actionability—Lessons from Colorectal Cancer Genes microsatellite instability DNA mismatch repair colorectal cancer hereditary syndrome immunotherapy microenviroment |
| title | Microsatellite Instability and Immune Response: From Microenvironment Features to Therapeutic Actionability—Lessons from Colorectal Cancer |
| title_full | Microsatellite Instability and Immune Response: From Microenvironment Features to Therapeutic Actionability—Lessons from Colorectal Cancer |
| title_fullStr | Microsatellite Instability and Immune Response: From Microenvironment Features to Therapeutic Actionability—Lessons from Colorectal Cancer |
| title_full_unstemmed | Microsatellite Instability and Immune Response: From Microenvironment Features to Therapeutic Actionability—Lessons from Colorectal Cancer |
| title_short | Microsatellite Instability and Immune Response: From Microenvironment Features to Therapeutic Actionability—Lessons from Colorectal Cancer |
| title_sort | microsatellite instability and immune response from microenvironment features to therapeutic actionability lessons from colorectal cancer |
| topic | microsatellite instability DNA mismatch repair colorectal cancer hereditary syndrome immunotherapy microenviroment |
| url | https://www.mdpi.com/2073-4425/14/6/1169 |
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