The Role of Somatic Mutations on the Immune Response of the Tumor Microenvironment in Prostate Cancer
Immunotherapy has improved patient survival in many types of cancer, but for prostate cancer, initial results with immunotherapy have been disappointing. Prostate cancer is considered an immunologically excluded or cold tumor, unable to generate an effective T-cell response against cancer cells. How...
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| Format: | Article |
| Language: | English |
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MDPI AG
2021-09-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/22/17/9550 |
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| author | Camila Morais Melo Thiago Vidotto Luiz Paulo Chaves William Lautert-Dutra Rodolfo Borges dos Reis Jeremy Andrew Squire |
| author_facet | Camila Morais Melo Thiago Vidotto Luiz Paulo Chaves William Lautert-Dutra Rodolfo Borges dos Reis Jeremy Andrew Squire |
| author_sort | Camila Morais Melo |
| collection | DOAJ |
| description | Immunotherapy has improved patient survival in many types of cancer, but for prostate cancer, initial results with immunotherapy have been disappointing. Prostate cancer is considered an immunologically excluded or cold tumor, unable to generate an effective T-cell response against cancer cells. However, a small but significant percentage of patients do respond to immunotherapy, suggesting that some specific molecular subtypes of this tumor may have a better response to checkpoint inhibitors. Recent findings suggest that, in addition to their function as cancer genes, somatic mutations of <i>PTEN</i>, <i>TP53</i>, <i>RB1</i>, <i>CDK12</i>, and DNA repair, or specific activation of regulatory pathways, such as ETS or MYC, may also facilitate immune evasion of the host response against cancer. This review presents an update of recent discoveries about the role that the common somatic mutations can play in changing the tumor microenvironment and immune response against prostate cancer. We describe how detailed molecular genetic analyses of the tumor microenvironment of prostate cancer using mouse models and human tumors are providing new insights into the cell types and pathways mediating immune responses. These analyses are helping researchers to design drug combinations that are more likely to target the molecular and immunological pathways that underlie treatment failure. |
| first_indexed | 2024-03-10T08:09:28Z |
| format | Article |
| id | doaj.art-17e04779afec4784bc38e0490f5c09ee |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T08:09:28Z |
| publishDate | 2021-09-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-17e04779afec4784bc38e0490f5c09ee2023-11-22T10:45:15ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-09-012217955010.3390/ijms22179550The Role of Somatic Mutations on the Immune Response of the Tumor Microenvironment in Prostate CancerCamila Morais Melo0Thiago Vidotto1Luiz Paulo Chaves2William Lautert-Dutra3Rodolfo Borges dos Reis4Jeremy Andrew Squire5Department of Genetics, Medicine School of Ribeirão Preto, University of São Paulo, Ribeirão Preto 14048-900, SP, BrazilDepartment of Genetics, Medicine School of Ribeirão Preto, University of São Paulo, Ribeirão Preto 14048-900, SP, BrazilDepartment of Genetics, Medicine School of Ribeirão Preto, University of São Paulo, Ribeirão Preto 14048-900, SP, BrazilDepartment of Genetics, Medicine School of Ribeirão Preto, University of São Paulo, Ribeirão Preto 14048-900, SP, BrazilDivision of Urology, Department of Surgery and Anatomy, Medicine School of Ribeirão Preto, University of São Paulo, Ribeirão Preto 14048-900, SP, BrazilDepartment of Genetics, Medicine School of Ribeirão Preto, University of São Paulo, Ribeirão Preto 14048-900, SP, BrazilImmunotherapy has improved patient survival in many types of cancer, but for prostate cancer, initial results with immunotherapy have been disappointing. Prostate cancer is considered an immunologically excluded or cold tumor, unable to generate an effective T-cell response against cancer cells. However, a small but significant percentage of patients do respond to immunotherapy, suggesting that some specific molecular subtypes of this tumor may have a better response to checkpoint inhibitors. Recent findings suggest that, in addition to their function as cancer genes, somatic mutations of <i>PTEN</i>, <i>TP53</i>, <i>RB1</i>, <i>CDK12</i>, and DNA repair, or specific activation of regulatory pathways, such as ETS or MYC, may also facilitate immune evasion of the host response against cancer. This review presents an update of recent discoveries about the role that the common somatic mutations can play in changing the tumor microenvironment and immune response against prostate cancer. We describe how detailed molecular genetic analyses of the tumor microenvironment of prostate cancer using mouse models and human tumors are providing new insights into the cell types and pathways mediating immune responses. These analyses are helping researchers to design drug combinations that are more likely to target the molecular and immunological pathways that underlie treatment failure.https://www.mdpi.com/1422-0067/22/17/9550immunotherapycheckpoint blockadeimmune evasioninnate and adaptive immune systemoncogenestumor suppressor genes |
| spellingShingle | Camila Morais Melo Thiago Vidotto Luiz Paulo Chaves William Lautert-Dutra Rodolfo Borges dos Reis Jeremy Andrew Squire The Role of Somatic Mutations on the Immune Response of the Tumor Microenvironment in Prostate Cancer International Journal of Molecular Sciences immunotherapy checkpoint blockade immune evasion innate and adaptive immune system oncogenes tumor suppressor genes |
| title | The Role of Somatic Mutations on the Immune Response of the Tumor Microenvironment in Prostate Cancer |
| title_full | The Role of Somatic Mutations on the Immune Response of the Tumor Microenvironment in Prostate Cancer |
| title_fullStr | The Role of Somatic Mutations on the Immune Response of the Tumor Microenvironment in Prostate Cancer |
| title_full_unstemmed | The Role of Somatic Mutations on the Immune Response of the Tumor Microenvironment in Prostate Cancer |
| title_short | The Role of Somatic Mutations on the Immune Response of the Tumor Microenvironment in Prostate Cancer |
| title_sort | role of somatic mutations on the immune response of the tumor microenvironment in prostate cancer |
| topic | immunotherapy checkpoint blockade immune evasion innate and adaptive immune system oncogenes tumor suppressor genes |
| url | https://www.mdpi.com/1422-0067/22/17/9550 |
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