Publicação
Immunogenicity of colorectal cancer with microsatellite instability
| Resumo: | Colorectal cancer (CRC) with microsatellite instability (MSI) constitutes a subset of CRC with a striking immunogenicity. Considering the two major pathways of colorectal tumorigenesis related to MSI, the Lynch syndrome and the serrated/methylated pathways, we can easily identify defects in the DNA mismatch repair (MMR) system causing loss of its function as the main drivers of the resultant MSI. This genetic condition predisposes the acquisition and accumulation of a great number of mutations, particularly in microsatellite sequences of coding gene regions, leading to the expression of tumour-specific neo-antigens. These peptides appear to induce an antitumoral immune response of the host. However, this same mutational mechanism may allow the development of immune evasion strategies by the tumour cells. The local tumour evasion mechanism seems to have prognostic implications and, paradoxically, might interfere with the ability of distant organ metastasis formation. Traditional determinants of CRC can correlate with the immunogenicity of the tumour. Immunogenomic stratification of CRC, as it will be presented in this review, would allow a better understanding of the potential of new therapeutic approaches in the area of immunotherapy regarding the immunological status of the tumour microenvironment. |
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| Autores principais: | Santos, Inês do Vale Costa |
| Assunto: | Colorectal Cancer Microsatellites Iinstability Immunogenicity Oncology |
| Ano: | 2017 |
| País: | Portugal |
| Tipo de documento: | dissertação de mestrado |
| Tipo de acesso: | acesso restrito |
| Instituição associada: | Universidade de Lisboa |
| Idioma: | inglês |
| Origem: | Repositório da Universidade de Lisboa |
| Resumo: | Colorectal cancer (CRC) with microsatellite instability (MSI) constitutes a subset of CRC with a striking immunogenicity. Considering the two major pathways of colorectal tumorigenesis related to MSI, the Lynch syndrome and the serrated/methylated pathways, we can easily identify defects in the DNA mismatch repair (MMR) system causing loss of its function as the main drivers of the resultant MSI. This genetic condition predisposes the acquisition and accumulation of a great number of mutations, particularly in microsatellite sequences of coding gene regions, leading to the expression of tumour-specific neo-antigens. These peptides appear to induce an antitumoral immune response of the host. However, this same mutational mechanism may allow the development of immune evasion strategies by the tumour cells. The local tumour evasion mechanism seems to have prognostic implications and, paradoxically, might interfere with the ability of distant organ metastasis formation. Traditional determinants of CRC can correlate with the immunogenicity of the tumour. Immunogenomic stratification of CRC, as it will be presented in this review, would allow a better understanding of the potential of new therapeutic approaches in the area of immunotherapy regarding the immunological status of the tumour microenvironment. |
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