Reduced T and NK Cell Activity in Glioblastoma Patients Correlates with TIM-3 and BAT3 Dysregulation
Inhibitory receptors are critical for regulating immune cell function. In cancer, these receptors are often over-expressed on the cell surface of T and NK cells, leading to reduced anti-tumor activity. Here, through the analysis of 11 commonly studied checkpoint and inhibitory receptors, we discern...
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MDPI AG
2024-10-01
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| author | Farah Ahmady Peter Curpen Louis Perriman Adilson Fonseca Teixeira Siqi Wu Hong-Jian Zhu Arpita Poddar Aparna Jayachandran George Kannourakis Rodney B. Luwor |
| author_facet | Farah Ahmady Peter Curpen Louis Perriman Adilson Fonseca Teixeira Siqi Wu Hong-Jian Zhu Arpita Poddar Aparna Jayachandran George Kannourakis Rodney B. Luwor |
| author_sort | Farah Ahmady |
| collection | DOAJ |
| description | Inhibitory receptors are critical for regulating immune cell function. In cancer, these receptors are often over-expressed on the cell surface of T and NK cells, leading to reduced anti-tumor activity. Here, through the analysis of 11 commonly studied checkpoint and inhibitory receptors, we discern that only <i>HAVCR2</i> (TIM3) and <i>ENTPD1</i> (CD39) display significantly greater gene expression in glioblastoma compared to normal brain and lower grade glioma. Cell surface TIM-3, but not ENTPD1, was also elevated on activated CD4<sup>+</sup> and CD8<sup>+</sup> T cells, as well as on NK cells from glioblastoma patients compared to healthy donor T and NK cells. A subsequent analysis of molecules known to co-ordinate TIM-3 function and regulation was performed, which revealed that BAT3 expression was significantly reduced in CD4<sup>+</sup> and CD8<sup>+</sup> T cells, as well as NK cells from glioblastoma patients compared to counterparts from healthy donors. These pro-inhibitory changes are also correlated with reduced levels of the activation marker CD69 and the pro-inflammatory cytokine IFNγ in CD4<sup>+</sup> and CD8<sup>+</sup> T cells, as well as NK cells from glioblastoma patients. Collectively, these data reveal that glioblastoma-mediated CD4<sup>+</sup> and CD8<sup>+</sup> T cell and NK cell suppression is due, at least in part, to dysregulated TIM-3 and BAT3 expression and the associated downstream immunoregulatory and dysfunctional effects. |
| format | Article |
| id | doaj-art-d967a9d4ac04450a94dbe014016bc1eb |
| institution | Kabale University |
| issn | 2073-4409 |
| language | English |
| publishDate | 2024-10-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj-art-d967a9d4ac04450a94dbe014016bc1eb2024-11-08T14:34:28ZengMDPI AGCells2073-44092024-10-011321177710.3390/cells13211777Reduced T and NK Cell Activity in Glioblastoma Patients Correlates with TIM-3 and BAT3 DysregulationFarah Ahmady0Peter Curpen1Louis Perriman2Adilson Fonseca Teixeira3Siqi Wu4Hong-Jian Zhu5Arpita Poddar6Aparna Jayachandran7George Kannourakis8Rodney B. Luwor9Fiona Elsey Cancer Research Institute, Ballarat, VIC 3350, AustraliaTownsville Hospital and Health Service, James Cook University, Townsville, QLD 4814, AustraliaFiona Elsey Cancer Research Institute, Ballarat, VIC 3350, AustraliaDepartment of Surgery, The Royal Melbourne Hospital, The University of Melbourne, Parkville, VIC 3050, AustraliaDepartment of Surgery, The Royal Melbourne Hospital, The University of Melbourne, Parkville, VIC 3050, AustraliaDepartment of Surgery, The Royal Melbourne Hospital, The University of Melbourne, Parkville, VIC 3050, AustraliaFiona Elsey Cancer Research Institute, Ballarat, VIC 3350, AustraliaFiona Elsey Cancer Research Institute, Ballarat, VIC 3350, AustraliaFiona Elsey Cancer Research Institute, Ballarat, VIC 3350, AustraliaFiona Elsey Cancer Research Institute, Ballarat, VIC 3350, AustraliaInhibitory receptors are critical for regulating immune cell function. In cancer, these receptors are often over-expressed on the cell surface of T and NK cells, leading to reduced anti-tumor activity. Here, through the analysis of 11 commonly studied checkpoint and inhibitory receptors, we discern that only <i>HAVCR2</i> (TIM3) and <i>ENTPD1</i> (CD39) display significantly greater gene expression in glioblastoma compared to normal brain and lower grade glioma. Cell surface TIM-3, but not ENTPD1, was also elevated on activated CD4<sup>+</sup> and CD8<sup>+</sup> T cells, as well as on NK cells from glioblastoma patients compared to healthy donor T and NK cells. A subsequent analysis of molecules known to co-ordinate TIM-3 function and regulation was performed, which revealed that BAT3 expression was significantly reduced in CD4<sup>+</sup> and CD8<sup>+</sup> T cells, as well as NK cells from glioblastoma patients compared to counterparts from healthy donors. These pro-inhibitory changes are also correlated with reduced levels of the activation marker CD69 and the pro-inflammatory cytokine IFNγ in CD4<sup>+</sup> and CD8<sup>+</sup> T cells, as well as NK cells from glioblastoma patients. Collectively, these data reveal that glioblastoma-mediated CD4<sup>+</sup> and CD8<sup>+</sup> T cell and NK cell suppression is due, at least in part, to dysregulated TIM-3 and BAT3 expression and the associated downstream immunoregulatory and dysfunctional effects.https://www.mdpi.com/2073-4409/13/21/1777TIM-3BAT3glioblastomaT cell exhaustion |
| spellingShingle | Farah Ahmady Peter Curpen Louis Perriman Adilson Fonseca Teixeira Siqi Wu Hong-Jian Zhu Arpita Poddar Aparna Jayachandran George Kannourakis Rodney B. Luwor Reduced T and NK Cell Activity in Glioblastoma Patients Correlates with TIM-3 and BAT3 Dysregulation Cells TIM-3 BAT3 glioblastoma T cell exhaustion |
| title | Reduced T and NK Cell Activity in Glioblastoma Patients Correlates with TIM-3 and BAT3 Dysregulation |
| title_full | Reduced T and NK Cell Activity in Glioblastoma Patients Correlates with TIM-3 and BAT3 Dysregulation |
| title_fullStr | Reduced T and NK Cell Activity in Glioblastoma Patients Correlates with TIM-3 and BAT3 Dysregulation |
| title_full_unstemmed | Reduced T and NK Cell Activity in Glioblastoma Patients Correlates with TIM-3 and BAT3 Dysregulation |
| title_short | Reduced T and NK Cell Activity in Glioblastoma Patients Correlates with TIM-3 and BAT3 Dysregulation |
| title_sort | reduced t and nk cell activity in glioblastoma patients correlates with tim 3 and bat3 dysregulation |
| topic | TIM-3 BAT3 glioblastoma T cell exhaustion |
| url | https://www.mdpi.com/2073-4409/13/21/1777 |
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