Interleukin-10 Induces Expression of Neuroendocrine Markers and PDL1 in Prostate Cancer Cells
Interleukin-10 (IL10) is best studied for its inhibitory action on immune cells and ability to suppress an antitumour immune response. But IL10 also exerts direct effects on nonimmune cells such as prostate cancer epithelial cells. Elevated serum levels of IL10 observed in prostate and other cancer...
Saved in:
| Main Authors: | , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Wiley
2020-01-01
|
| Series: | Prostate Cancer |
| Online Access: | http://dx.doi.org/10.1155/2020/5305306 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1849684929060798464 |
|---|---|
| author | Abrar Samiea Jeff S. J. Yoon Christopher J. Ong Amina Zoubeidi Thomas C. Chamberlain Alice L.-F. Mui |
| author_facet | Abrar Samiea Jeff S. J. Yoon Christopher J. Ong Amina Zoubeidi Thomas C. Chamberlain Alice L.-F. Mui |
| author_sort | Abrar Samiea |
| collection | DOAJ |
| description | Interleukin-10 (IL10) is best studied for its inhibitory action on immune cells and ability to suppress an antitumour immune response. But IL10 also exerts direct effects on nonimmune cells such as prostate cancer epithelial cells. Elevated serum levels of IL10 observed in prostate and other cancer patients are associated with poor prognosis. After first-line androgen-deprivation therapy, prostate cancer patients are treated with androgen receptor antagonists such as enzalutamide to inhibit androgen-dependent prostate cancer cell growth. However, development of resistance inevitably occurs and this is associated with tumour differentiation to more aggressive forms such as a neuroendocrine phenotype characterized by expression of neuron specific enolase and synaptophysin. We found that treatment of prostate cancer cell lines in vitro with IL10 or enzalutamide induced markers of neuroendocrine differentiation and inhibited androgen receptor reporter activity. Both also upregulated the levels of PDL1, which could promote tumour survival in vivo through its interaction with the immune cell inhibitory receptor PD1 to suppress antitumour immunity. These findings suggest that IL10’s direct action on prostate cancer cells could contribute to prostate cancer progression independent of IL10’s suppression of host immune cells. |
| format | Article |
| id | doaj-art-bc6b7ee61bac411b9c6eba4813cc37ea |
| institution | DOAJ |
| issn | 2090-3111 2090-312X |
| language | English |
| publishDate | 2020-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Prostate Cancer |
| spelling | doaj-art-bc6b7ee61bac411b9c6eba4813cc37ea2025-08-20T03:23:19ZengWileyProstate Cancer2090-31112090-312X2020-01-01202010.1155/2020/53053065305306Interleukin-10 Induces Expression of Neuroendocrine Markers and PDL1 in Prostate Cancer CellsAbrar Samiea0Jeff S. J. Yoon1Christopher J. Ong2Amina Zoubeidi3Thomas C. Chamberlain4Alice L.-F. Mui5Immunity and Infection Research Centre, Vancouver Coastal Health Research Institute, Vancouver, CanadaImmunity and Infection Research Centre, Vancouver Coastal Health Research Institute, Vancouver, CanadaDepartment of Surgery, University of British Columbia, Vancouver, CanadaVancouver Prostate Centre and Department of Urologic Sciences, University of British Columbia, Vancouver, BC, CanadaImmunity and Infection Research Centre, Vancouver Coastal Health Research Institute, Vancouver, CanadaImmunity and Infection Research Centre, Vancouver Coastal Health Research Institute, Vancouver, CanadaInterleukin-10 (IL10) is best studied for its inhibitory action on immune cells and ability to suppress an antitumour immune response. But IL10 also exerts direct effects on nonimmune cells such as prostate cancer epithelial cells. Elevated serum levels of IL10 observed in prostate and other cancer patients are associated with poor prognosis. After first-line androgen-deprivation therapy, prostate cancer patients are treated with androgen receptor antagonists such as enzalutamide to inhibit androgen-dependent prostate cancer cell growth. However, development of resistance inevitably occurs and this is associated with tumour differentiation to more aggressive forms such as a neuroendocrine phenotype characterized by expression of neuron specific enolase and synaptophysin. We found that treatment of prostate cancer cell lines in vitro with IL10 or enzalutamide induced markers of neuroendocrine differentiation and inhibited androgen receptor reporter activity. Both also upregulated the levels of PDL1, which could promote tumour survival in vivo through its interaction with the immune cell inhibitory receptor PD1 to suppress antitumour immunity. These findings suggest that IL10’s direct action on prostate cancer cells could contribute to prostate cancer progression independent of IL10’s suppression of host immune cells.http://dx.doi.org/10.1155/2020/5305306 |
| spellingShingle | Abrar Samiea Jeff S. J. Yoon Christopher J. Ong Amina Zoubeidi Thomas C. Chamberlain Alice L.-F. Mui Interleukin-10 Induces Expression of Neuroendocrine Markers and PDL1 in Prostate Cancer Cells Prostate Cancer |
| title | Interleukin-10 Induces Expression of Neuroendocrine Markers and PDL1 in Prostate Cancer Cells |
| title_full | Interleukin-10 Induces Expression of Neuroendocrine Markers and PDL1 in Prostate Cancer Cells |
| title_fullStr | Interleukin-10 Induces Expression of Neuroendocrine Markers and PDL1 in Prostate Cancer Cells |
| title_full_unstemmed | Interleukin-10 Induces Expression of Neuroendocrine Markers and PDL1 in Prostate Cancer Cells |
| title_short | Interleukin-10 Induces Expression of Neuroendocrine Markers and PDL1 in Prostate Cancer Cells |
| title_sort | interleukin 10 induces expression of neuroendocrine markers and pdl1 in prostate cancer cells |
| url | http://dx.doi.org/10.1155/2020/5305306 |
| work_keys_str_mv | AT abrarsamiea interleukin10inducesexpressionofneuroendocrinemarkersandpdl1inprostatecancercells AT jeffsjyoon interleukin10inducesexpressionofneuroendocrinemarkersandpdl1inprostatecancercells AT christopherjong interleukin10inducesexpressionofneuroendocrinemarkersandpdl1inprostatecancercells AT aminazoubeidi interleukin10inducesexpressionofneuroendocrinemarkersandpdl1inprostatecancercells AT thomascchamberlain interleukin10inducesexpressionofneuroendocrinemarkersandpdl1inprostatecancercells AT alicelfmui interleukin10inducesexpressionofneuroendocrinemarkersandpdl1inprostatecancercells |