Genomic and Immunologic Correlates of Indoleamine 2,3-Dioxygenase Pathway Expression in Cancer
Immune checkpoint blockade leads to unprecedented responses in many cancer types. An alternative method of unleashing anti-tumor immune response is to target immunosuppressive metabolic pathways like the indoleamine 2,3-dioxygenase (IDO) pathway. Despite promising results in Phase I/II clinical tria...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2021-07-01
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| Series: | Frontiers in Genetics |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fgene.2021.706435/full |
| _version_ | 1818453006674296832 |
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| author | Anshuman Panda Shridar Ganesan Shridar Ganesan |
| author_facet | Anshuman Panda Shridar Ganesan Shridar Ganesan |
| author_sort | Anshuman Panda |
| collection | DOAJ |
| description | Immune checkpoint blockade leads to unprecedented responses in many cancer types. An alternative method of unleashing anti-tumor immune response is to target immunosuppressive metabolic pathways like the indoleamine 2,3-dioxygenase (IDO) pathway. Despite promising results in Phase I/II clinical trials, an IDO-1 inhibitor did not show clinical benefit in a Phase III clinical trial. Since, a treatment can be quite effective in a specific subset without being effective in the whole cancer type, it is important to identify the subsets of cancers that may benefit from IDO-1 inhibitors. In this study, we looked for the genomic and immunologic correlates of IDO pathway expression in cancer using the Cancer Genome Atlas (TCGA) dataset. Strong CD8+ T-cell infiltration, high mutation burden, and expression of exogenous viruses [Epstein-Barr virus (EBV), Human papilloma virus (HPV), and Hepatitis C virus (HCV)] or endogenous retrovirus (ERV3-2) were associated with over-expression of IDO-1 in most cancer types, IDO-2 in many cancer types, and TDO-2 in a few cancer types. High mutation burden in ER+ HER2− breast cancer, and ERV3-2 expression in ER− HER2− and HER2+ breast, colon, and endometrial cancers were associated with over-expression of all three genes. These results may have important implications for guiding development clinical trials of IDO-1 inhibitors. |
| first_indexed | 2024-12-14T21:32:08Z |
| format | Article |
| id | doaj.art-5a996b90721940c5914d2c54661b9066 |
| institution | Directory Open Access Journal |
| issn | 1664-8021 |
| language | English |
| last_indexed | 2024-12-14T21:32:08Z |
| publishDate | 2021-07-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Genetics |
| spelling | doaj.art-5a996b90721940c5914d2c54661b90662022-12-21T22:46:40ZengFrontiers Media S.A.Frontiers in Genetics1664-80212021-07-011210.3389/fgene.2021.706435706435Genomic and Immunologic Correlates of Indoleamine 2,3-Dioxygenase Pathway Expression in CancerAnshuman Panda0Shridar Ganesan1Shridar Ganesan2Department of Medical Oncology, Rutgers Cancer Institute of New Jersey, New Brunswick, NJ, United StatesDepartment of Medical Oncology, Rutgers Cancer Institute of New Jersey, New Brunswick, NJ, United StatesDepartment of Medicine, Rutgers Robert Wood Johnson Medical School, New Brunswick, NJ, United StatesImmune checkpoint blockade leads to unprecedented responses in many cancer types. An alternative method of unleashing anti-tumor immune response is to target immunosuppressive metabolic pathways like the indoleamine 2,3-dioxygenase (IDO) pathway. Despite promising results in Phase I/II clinical trials, an IDO-1 inhibitor did not show clinical benefit in a Phase III clinical trial. Since, a treatment can be quite effective in a specific subset without being effective in the whole cancer type, it is important to identify the subsets of cancers that may benefit from IDO-1 inhibitors. In this study, we looked for the genomic and immunologic correlates of IDO pathway expression in cancer using the Cancer Genome Atlas (TCGA) dataset. Strong CD8+ T-cell infiltration, high mutation burden, and expression of exogenous viruses [Epstein-Barr virus (EBV), Human papilloma virus (HPV), and Hepatitis C virus (HCV)] or endogenous retrovirus (ERV3-2) were associated with over-expression of IDO-1 in most cancer types, IDO-2 in many cancer types, and TDO-2 in a few cancer types. High mutation burden in ER+ HER2− breast cancer, and ERV3-2 expression in ER− HER2− and HER2+ breast, colon, and endometrial cancers were associated with over-expression of all three genes. These results may have important implications for guiding development clinical trials of IDO-1 inhibitors.https://www.frontiersin.org/articles/10.3389/fgene.2021.706435/fullIDO1 inhibitorIDO2TDO2immune checkpoint inhibitorsCD8+ T-celltumor mutation burden |
| spellingShingle | Anshuman Panda Shridar Ganesan Shridar Ganesan Genomic and Immunologic Correlates of Indoleamine 2,3-Dioxygenase Pathway Expression in Cancer Frontiers in Genetics IDO1 inhibitor IDO2 TDO2 immune checkpoint inhibitors CD8+ T-cell tumor mutation burden |
| title | Genomic and Immunologic Correlates of Indoleamine 2,3-Dioxygenase Pathway Expression in Cancer |
| title_full | Genomic and Immunologic Correlates of Indoleamine 2,3-Dioxygenase Pathway Expression in Cancer |
| title_fullStr | Genomic and Immunologic Correlates of Indoleamine 2,3-Dioxygenase Pathway Expression in Cancer |
| title_full_unstemmed | Genomic and Immunologic Correlates of Indoleamine 2,3-Dioxygenase Pathway Expression in Cancer |
| title_short | Genomic and Immunologic Correlates of Indoleamine 2,3-Dioxygenase Pathway Expression in Cancer |
| title_sort | genomic and immunologic correlates of indoleamine 2 3 dioxygenase pathway expression in cancer |
| topic | IDO1 inhibitor IDO2 TDO2 immune checkpoint inhibitors CD8+ T-cell tumor mutation burden |
| url | https://www.frontiersin.org/articles/10.3389/fgene.2021.706435/full |
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