Hepatic Tumor Microenvironments and Effects on NK Cell Phenotype and Function
The liver is a complex organ with critical physiological functions including metabolism, glucose storage, and drug detoxification. Its unique immune profile with large numbers of cytotoxic CD8<sup>+</sup> T cells and significant innate lymphoid population, including natural killer cells,...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
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MDPI AG
2019-08-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/20/17/4131 |
| _version_ | 1811237194232233984 |
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| author | Julián Piñeiro Fernández Kimberly A. Luddy Cathal Harmon Cliona O’Farrelly |
| author_facet | Julián Piñeiro Fernández Kimberly A. Luddy Cathal Harmon Cliona O’Farrelly |
| author_sort | Julián Piñeiro Fernández |
| collection | DOAJ |
| description | The liver is a complex organ with critical physiological functions including metabolism, glucose storage, and drug detoxification. Its unique immune profile with large numbers of cytotoxic CD8<sup>+</sup> T cells and significant innate lymphoid population, including natural killer cells, <inline-formula> <math display="inline"> <semantics> <mrow> <mi>γ</mi> <mi>δ</mi> </mrow> </semantics> </math> </inline-formula> T cells, MAIT cells, and iNKTcells, suggests an important anti-tumor surveillance role. Despite significant immune surveillance in the liver, in particular large NK cell populations, hepatic cell carcinoma (HCC) is a relatively common outcome of chronic liver infection or inflammation. The liver is also the second most common site of metastatic disease. This discordance suggests immune suppression by the environments of primary and secondary liver cancers. Classic tumor microenvironments (TME) are poorly perfused, leading to accumulation of tumor cell metabolites, diminished O<sub>2</sub>, and decreased nutrient levels, all of which impact immune cell phenotype and function. Here, we focus on changes in the liver microenvironment associated with tumor presence and how they affect NK function and phenotype. |
| first_indexed | 2024-04-12T12:21:55Z |
| format | Article |
| id | doaj.art-3169b32d7d3e4ec397364d597a7e2873 |
| institution | Directory Open Access Journal |
| issn | 1422-0067 |
| language | English |
| last_indexed | 2024-04-12T12:21:55Z |
| publishDate | 2019-08-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-3169b32d7d3e4ec397364d597a7e28732022-12-22T03:33:17ZengMDPI AGInternational Journal of Molecular Sciences1422-00672019-08-012017413110.3390/ijms20174131ijms20174131Hepatic Tumor Microenvironments and Effects on NK Cell Phenotype and FunctionJulián Piñeiro Fernández0Kimberly A. Luddy1Cathal Harmon2Cliona O’Farrelly3School of Biochemistry and Immunology, Trinity College Dublin, D02 PN40 Dublin, IrelandSchool of Biochemistry and Immunology, Trinity College Dublin, D02 PN40 Dublin, IrelandBrigham and Women’s Hospital, Harvard Institutes of Medicine, Harvard Medical School, Boston, MA 02138, USASchool of Biochemistry and Immunology, Trinity College Dublin, D02 PN40 Dublin, IrelandThe liver is a complex organ with critical physiological functions including metabolism, glucose storage, and drug detoxification. Its unique immune profile with large numbers of cytotoxic CD8<sup>+</sup> T cells and significant innate lymphoid population, including natural killer cells, <inline-formula> <math display="inline"> <semantics> <mrow> <mi>γ</mi> <mi>δ</mi> </mrow> </semantics> </math> </inline-formula> T cells, MAIT cells, and iNKTcells, suggests an important anti-tumor surveillance role. Despite significant immune surveillance in the liver, in particular large NK cell populations, hepatic cell carcinoma (HCC) is a relatively common outcome of chronic liver infection or inflammation. The liver is also the second most common site of metastatic disease. This discordance suggests immune suppression by the environments of primary and secondary liver cancers. Classic tumor microenvironments (TME) are poorly perfused, leading to accumulation of tumor cell metabolites, diminished O<sub>2</sub>, and decreased nutrient levels, all of which impact immune cell phenotype and function. Here, we focus on changes in the liver microenvironment associated with tumor presence and how they affect NK function and phenotype.https://www.mdpi.com/1422-0067/20/17/4131liverNK cellscolorectal cancercolorectal liver metastasistumor microenvironmentexhaustionhypoxialactic acidadenosinetryptophanimmune checkpointshepatocellular carcinomaimmunometabolism |
| spellingShingle | Julián Piñeiro Fernández Kimberly A. Luddy Cathal Harmon Cliona O’Farrelly Hepatic Tumor Microenvironments and Effects on NK Cell Phenotype and Function International Journal of Molecular Sciences liver NK cells colorectal cancer colorectal liver metastasis tumor microenvironment exhaustion hypoxia lactic acid adenosine tryptophan immune checkpoints hepatocellular carcinoma immunometabolism |
| title | Hepatic Tumor Microenvironments and Effects on NK Cell Phenotype and Function |
| title_full | Hepatic Tumor Microenvironments and Effects on NK Cell Phenotype and Function |
| title_fullStr | Hepatic Tumor Microenvironments and Effects on NK Cell Phenotype and Function |
| title_full_unstemmed | Hepatic Tumor Microenvironments and Effects on NK Cell Phenotype and Function |
| title_short | Hepatic Tumor Microenvironments and Effects on NK Cell Phenotype and Function |
| title_sort | hepatic tumor microenvironments and effects on nk cell phenotype and function |
| topic | liver NK cells colorectal cancer colorectal liver metastasis tumor microenvironment exhaustion hypoxia lactic acid adenosine tryptophan immune checkpoints hepatocellular carcinoma immunometabolism |
| url | https://www.mdpi.com/1422-0067/20/17/4131 |
| work_keys_str_mv | AT julianpineirofernandez hepatictumormicroenvironmentsandeffectsonnkcellphenotypeandfunction AT kimberlyaluddy hepatictumormicroenvironmentsandeffectsonnkcellphenotypeandfunction AT cathalharmon hepatictumormicroenvironmentsandeffectsonnkcellphenotypeandfunction AT clionaofarrelly hepatictumormicroenvironmentsandeffectsonnkcellphenotypeandfunction |