Implications of hereditary origin on the immune phenotype of mismatch repair-deficient cancers: systematic literature review
Microsatellite instability (MSI) represents one of the major types of genomic instability in human cancers and is most common in colorectal cancer (CRC) and endometrial cancer (EC). MSI develops as a consequence of DNA mismatch repair (MMR) deficiency, which can occur sporadically or in the context...
Gespeichert in:
| Hauptverfasser: | , , , |
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| Dokumenttyp: | Article (Journal) |
| Sprache: | Englisch |
| Veröffentlicht: |
4 June 2020
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| In: |
Journal of Clinical Medicine
Year: 2020, Jahrgang: 9, Heft: 6, Pages: 1-20 |
| ISSN: | 2077-0383 |
| DOI: | 10.3390/jcm9061741 |
| Online-Zugang: | Verlag, kostenfrei, Volltext: https://doi.org/10.3390/jcm9061741 Verlag, kostenfrei, Volltext: https://www.mdpi.com/2077-0383/9/6/1741 
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| Verfasserangaben: | Lena Bohaumilitzky, Magnus von Knebel Doeberitz, Matthias Kloor and Aysel Ahadova |
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| 245 | 1 | 0 | |a Implications of hereditary origin on the immune phenotype of mismatch repair-deficient cancers |b systematic literature review |c Lena Bohaumilitzky, Magnus von Knebel Doeberitz, Matthias Kloor and Aysel Ahadova |
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| 520 | |a Microsatellite instability (MSI) represents one of the major types of genomic instability in human cancers and is most common in colorectal cancer (CRC) and endometrial cancer (EC). MSI develops as a consequence of DNA mismatch repair (MMR) deficiency, which can occur sporadically or in the context of Lynch syndrome (LS), the most common inherited tumor syndrome. MMR deficiency triggers the accumulation of high numbers of somatic mutations in the affected cells, mostly indel mutations at microsatellite sequences. MSI tumors are among the most immunogenic human tumors and are often characterized by pronounced local immune responses. However, so far, little is known about immunological differences between sporadic and hereditary MSI tumors. Therefore, a systematic literature search was conducted to comprehensively collect data on the differences in local T cell infiltration and immune evasion mechanisms between sporadic and LS-associated MSI tumors. The vast majority of collected studies were focusing on CRC and EC. Generally, more pronounced T cell infiltration and a higher frequency of B2M mutations were reported for LS-associated compared to sporadic MSI tumors. In addition, phenotypic features associated with enhanced lymphocyte recruitment were reported to be specifically associated with hereditary MSI CRCs. The quantitative and qualitative differences clearly indicate a distinct biology of sporadic and hereditary MSI tumors. Clinically, these findings underline the need for differentiating sporadic and hereditary tumors in basic science studies and clinical trials, including trials evaluating immune checkpoint blockade therapy in MSI tumors. | ||
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| 650 | 4 | |a microsatellite instability | |
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