High Levels of PD-L1+ and Hyal2+ Myeloid-derived Suppressor Cells in Renal Cell Carcinoma
Renal cell carcinoma (RCC) patients frequently have increased number of immunosuppressive myeloid cells in circulation. High number of myeloid-derived suppressor cells (MDSCs) in the blood are associated with immune suppression as well as with cancer-related inflammation which drives the mobilizati...
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| Format: | Article |
| Language: | English |
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Codon Publications
2022-04-01
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| Series: | Journal of Kidney Cancer and VHL |
| Subjects: | |
| Online Access: | https://jkcvhl.com/index.php/jkcvhl/article/view/208 |
| _version_ | 1811234127771336704 |
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| author | Sergei Kusmartsev Elizabeth Kwenda Paul R. Dominguez-Gutierrez Paul L. Crispen Padraic O’Malley |
| author_facet | Sergei Kusmartsev Elizabeth Kwenda Paul R. Dominguez-Gutierrez Paul L. Crispen Padraic O’Malley |
| author_sort | Sergei Kusmartsev |
| collection | DOAJ |
| description |
Renal cell carcinoma (RCC) patients frequently have increased number of immunosuppressive myeloid cells in circulation. High number of myeloid-derived suppressor cells (MDSCs) in the blood are associated with immune suppression as well as with cancer-related inflammation which drives the mobilization of myeloid cells to tumor tissue. Here, we show that peripheral blood from a previously untreated RCC patient has increased the number of monocytic CD33+CD11b+ MDSCs, which also co-expressed PD-L1 and membrane-bound enzyme hyaluronidase 2 (Hyal2). PD-L1 expression is associated with immune suppression, whereas expression of Hyal2 is associated with inflammation, because Hyal2+ myeloid cells can degrade the extracellular hyaluronan (HA), leading to the accumulation of pro-inflammatory HA fragments with low molecular weight. These findings implicate the potential involvement of monocytic MDSCs in both tumor-associated immune suppression and cancer-related inflammation. Analysis of organotypic tumor-tissue slice cultures prepared from cancer tissue of the same patient revealed the significant presence of PD-L1+ HLA-DR+ macrophage-like or dendritic cell-like antigen-presenting cells in tumor stroma. Interestingly, stroma-associated PD-L1+ cells frequently have intracellular hyaluronan. Collectively, data presented in this study suggest that the interplay between tumor-recruited myeloid cells and stromal HA may contribute to the inflammation and immune tolerance in kidney cancer.
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| first_indexed | 2024-04-12T11:31:26Z |
| format | Article |
| id | doaj.art-b4bfdd8a3a5f4164a440fd2371c2653d |
| institution | Directory Open Access Journal |
| issn | 2203-5826 |
| language | English |
| last_indexed | 2024-04-12T11:31:26Z |
| publishDate | 2022-04-01 |
| publisher | Codon Publications |
| record_format | Article |
| series | Journal of Kidney Cancer and VHL |
| spelling | doaj.art-b4bfdd8a3a5f4164a440fd2371c2653d2022-12-22T03:35:01ZengCodon PublicationsJournal of Kidney Cancer and VHL2203-58262022-04-019210.15586/jkcvhl.v9i2.208High Levels of PD-L1+ and Hyal2+ Myeloid-derived Suppressor Cells in Renal Cell CarcinomaSergei Kusmartsev0Elizabeth Kwenda1Paul R. Dominguez-Gutierrez2Paul L. Crispen3Padraic O’Malley4Department of Urology, University of Florida, Gainesville, FL, USA.Department of Urology, University of Florida, Gainesville, FL, USA.Department of Urology, University of Florida, Gainesville, FL, USA.Department of Urology, University of Florida, Gainesville, FL, USA.Department of Urology, University of Florida, Gainesville, FL, USA. Renal cell carcinoma (RCC) patients frequently have increased number of immunosuppressive myeloid cells in circulation. High number of myeloid-derived suppressor cells (MDSCs) in the blood are associated with immune suppression as well as with cancer-related inflammation which drives the mobilization of myeloid cells to tumor tissue. Here, we show that peripheral blood from a previously untreated RCC patient has increased the number of monocytic CD33+CD11b+ MDSCs, which also co-expressed PD-L1 and membrane-bound enzyme hyaluronidase 2 (Hyal2). PD-L1 expression is associated with immune suppression, whereas expression of Hyal2 is associated with inflammation, because Hyal2+ myeloid cells can degrade the extracellular hyaluronan (HA), leading to the accumulation of pro-inflammatory HA fragments with low molecular weight. These findings implicate the potential involvement of monocytic MDSCs in both tumor-associated immune suppression and cancer-related inflammation. Analysis of organotypic tumor-tissue slice cultures prepared from cancer tissue of the same patient revealed the significant presence of PD-L1+ HLA-DR+ macrophage-like or dendritic cell-like antigen-presenting cells in tumor stroma. Interestingly, stroma-associated PD-L1+ cells frequently have intracellular hyaluronan. Collectively, data presented in this study suggest that the interplay between tumor-recruited myeloid cells and stromal HA may contribute to the inflammation and immune tolerance in kidney cancer. https://jkcvhl.com/index.php/jkcvhl/article/view/208renal cell carcinomacancer immune microenvironmentmyeloid-derived suppressor cellsHyal2 |
| spellingShingle | Sergei Kusmartsev Elizabeth Kwenda Paul R. Dominguez-Gutierrez Paul L. Crispen Padraic O’Malley High Levels of PD-L1+ and Hyal2+ Myeloid-derived Suppressor Cells in Renal Cell Carcinoma Journal of Kidney Cancer and VHL renal cell carcinoma cancer immune microenvironment myeloid-derived suppressor cells Hyal2 |
| title | High Levels of PD-L1+ and Hyal2+ Myeloid-derived Suppressor Cells in Renal Cell Carcinoma |
| title_full | High Levels of PD-L1+ and Hyal2+ Myeloid-derived Suppressor Cells in Renal Cell Carcinoma |
| title_fullStr | High Levels of PD-L1+ and Hyal2+ Myeloid-derived Suppressor Cells in Renal Cell Carcinoma |
| title_full_unstemmed | High Levels of PD-L1+ and Hyal2+ Myeloid-derived Suppressor Cells in Renal Cell Carcinoma |
| title_short | High Levels of PD-L1+ and Hyal2+ Myeloid-derived Suppressor Cells in Renal Cell Carcinoma |
| title_sort | high levels of pd l1 and hyal2 myeloid derived suppressor cells in renal cell carcinoma |
| topic | renal cell carcinoma cancer immune microenvironment myeloid-derived suppressor cells Hyal2 |
| url | https://jkcvhl.com/index.php/jkcvhl/article/view/208 |
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