Presence of regulatory T-cells in endometrial cancer predicts poorer overall survival and promotes progression of tumor cells
Purpose Endometrial cancer (EC) is one of the most common gynaecologic malignancies. Tumor infiltrating regulatory T-cells (Treg) have been reported to have a prognostic impact in many malignancies. Immunotherapeutic strategies are gaining interest for advanced and recurrent EC cases, where treatmen...
Ausführliche Beschreibung
Gespeichert in:
| Autor*in: |
Kolben, Thomas [verfasserIn] |
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| Format: |
E-Artikel |
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| Sprache: |
Englisch |
| Erschienen: |
2022 |
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| Schlagwörter: |
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| Anmerkung: |
© The Author(s) 2022 |
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| Übergeordnetes Werk: |
Enthalten in: Cellular oncology - Amsterdam [u.a.] : IOS Press, 2004, 45(2022), 6 vom: 13. Sept., Seite 1171-1185 |
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| Übergeordnetes Werk: |
volume:45 ; year:2022 ; number:6 ; day:13 ; month:09 ; pages:1171-1185 |
| Links: |
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| DOI / URN: |
10.1007/s13402-022-00708-2 |
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SPR048871311 |
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| 100 | 1 | |a Kolben, Thomas |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Presence of regulatory T-cells in endometrial cancer predicts poorer overall survival and promotes progression of tumor cells |
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| 520 | |a Purpose Endometrial cancer (EC) is one of the most common gynaecologic malignancies. Tumor infiltrating regulatory T-cells (Treg) have been reported to have a prognostic impact in many malignancies. Immunotherapeutic strategies are gaining interest for advanced and recurrent EC cases, where treatment options are rare. Our study was aimed at determining the value of Treg in EC progression. Methods EC specimens from 275 patients and 28 controls were screened immunohistochemically for the presence of Treg represented by FoxP3. Correlations with clinicopathological and survival parameters were performed. Functional assays were performed using EC cell lines Ishikawa + and RL95-2 after co-culturing with isolated CD4 + CD25 + CD127dim Treg. To assess the influence of EC on the composition of peripheral blood mononuclear cells (PBMC), flow cytometric analyses were performed. Results We found that an increased infiltration of Treg was associated with high grades and a reduced overall survival. Treg were almost absent in endometrium tissues from healthy control patients. Co-culture of tumor cells with CD4 + CD25 + CD127dim Treg led to functional changes: enhanced invasion, migration and viability indicated that increased levels of Treg in the tumor microenvironment may promote tumor growth. Furthermore, we found that the presence of EC cells led to phenotypic changes in PBMC, showing significantly increased levels of CD25 and FoxP3. Conclusion Our results indicate that the presence of Treg in the EC tumor environment is associated with a poorer outcome. A remarkable impact of Treg on tumor cell behaviour and vice versa of tumor cells on PBMC subpopulations support this notion mechanistically. Our findings provide a basis for focusing on Treg as potential future therapeutic targets in EC. | ||
| 650 | 4 | |a Endometrial cancer |7 (dpeaa)DE-He213 | |
| 650 | 4 | |a Regulatory T-cells |7 (dpeaa)DE-He213 | |
| 650 | 4 | |a FoxP3 |7 (dpeaa)DE-He213 | |
| 650 | 4 | |a Immune escape |7 (dpeaa)DE-He213 | |
| 650 | 4 | |a Survival |7 (dpeaa)DE-He213 | |
| 700 | 1 | |a Mannewitz, Mareike |4 aut | |
| 700 | 1 | |a Perleberg, Carolin |4 aut | |
| 700 | 1 | |a Schnell, Konstantin |4 aut | |
| 700 | 1 | |a Anz, David |4 aut | |
| 700 | 1 | |a Hahn, Laura |4 aut | |
| 700 | 1 | |a Meister, Sarah |4 aut | |
| 700 | 1 | |a Schmoeckel, Elisa |4 aut | |
| 700 | 1 | |a Burges, Alexander |4 aut | |
| 700 | 1 | |a Czogalla, Bastian |4 aut | |
| 700 | 1 | |a Hester, Anna |4 aut | |
| 700 | 1 | |a Mahner, Sven |4 aut | |
| 700 | 1 | |a Kessler, Mirjana |4 aut | |
| 700 | 1 | |a Jeschke, Udo |4 aut | |
| 700 | 1 | |a Corradini, Stefanie |4 aut | |
| 700 | 1 | |a Trillsch, Fabian |4 aut | |
| 700 | 1 | |a Beyer, Susanne |4 aut | |
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10.1007/s13402-022-00708-2 doi (DE-627)SPR048871311 (SPR)s13402-022-00708-2-e DE-627 ger DE-627 rakwb eng Kolben, Thomas verfasserin aut Presence of regulatory T-cells in endometrial cancer predicts poorer overall survival and promotes progression of tumor cells 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s) 2022 Purpose Endometrial cancer (EC) is one of the most common gynaecologic malignancies. Tumor infiltrating regulatory T-cells (Treg) have been reported to have a prognostic impact in many malignancies. Immunotherapeutic strategies are gaining interest for advanced and recurrent EC cases, where treatment options are rare. Our study was aimed at determining the value of Treg in EC progression. Methods EC specimens from 275 patients and 28 controls were screened immunohistochemically for the presence of Treg represented by FoxP3. Correlations with clinicopathological and survival parameters were performed. Functional assays were performed using EC cell lines Ishikawa + and RL95-2 after co-culturing with isolated CD4 + CD25 + CD127dim Treg. To assess the influence of EC on the composition of peripheral blood mononuclear cells (PBMC), flow cytometric analyses were performed. Results We found that an increased infiltration of Treg was associated with high grades and a reduced overall survival. Treg were almost absent in endometrium tissues from healthy control patients. Co-culture of tumor cells with CD4 + CD25 + CD127dim Treg led to functional changes: enhanced invasion, migration and viability indicated that increased levels of Treg in the tumor microenvironment may promote tumor growth. Furthermore, we found that the presence of EC cells led to phenotypic changes in PBMC, showing significantly increased levels of CD25 and FoxP3. Conclusion Our results indicate that the presence of Treg in the EC tumor environment is associated with a poorer outcome. A remarkable impact of Treg on tumor cell behaviour and vice versa of tumor cells on PBMC subpopulations support this notion mechanistically. Our findings provide a basis for focusing on Treg as potential future therapeutic targets in EC. Endometrial cancer (dpeaa)DE-He213 Regulatory T-cells (dpeaa)DE-He213 FoxP3 (dpeaa)DE-He213 Immune escape (dpeaa)DE-He213 Survival (dpeaa)DE-He213 Mannewitz, Mareike aut Perleberg, Carolin aut Schnell, Konstantin aut Anz, David aut Hahn, Laura aut Meister, Sarah aut Schmoeckel, Elisa aut Burges, Alexander aut Czogalla, Bastian aut Hester, Anna aut Mahner, Sven aut Kessler, Mirjana aut Jeschke, Udo aut Corradini, Stefanie aut Trillsch, Fabian aut Beyer, Susanne aut Enthalten in Cellular oncology Amsterdam [u.a.] : IOS Press, 2004 45(2022), 6 vom: 13. Sept., Seite 1171-1185 (DE-627)392964430 (DE-600)2158254-3 1875-8606 nnns volume:45 year:2022 number:6 day:13 month:09 pages:1171-1185 https://dx.doi.org/10.1007/s13402-022-00708-2 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_702 AR 45 2022 6 13 09 1171-1185 |
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10.1007/s13402-022-00708-2 doi (DE-627)SPR048871311 (SPR)s13402-022-00708-2-e DE-627 ger DE-627 rakwb eng Kolben, Thomas verfasserin aut Presence of regulatory T-cells in endometrial cancer predicts poorer overall survival and promotes progression of tumor cells 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s) 2022 Purpose Endometrial cancer (EC) is one of the most common gynaecologic malignancies. Tumor infiltrating regulatory T-cells (Treg) have been reported to have a prognostic impact in many malignancies. Immunotherapeutic strategies are gaining interest for advanced and recurrent EC cases, where treatment options are rare. Our study was aimed at determining the value of Treg in EC progression. Methods EC specimens from 275 patients and 28 controls were screened immunohistochemically for the presence of Treg represented by FoxP3. Correlations with clinicopathological and survival parameters were performed. Functional assays were performed using EC cell lines Ishikawa + and RL95-2 after co-culturing with isolated CD4 + CD25 + CD127dim Treg. To assess the influence of EC on the composition of peripheral blood mononuclear cells (PBMC), flow cytometric analyses were performed. Results We found that an increased infiltration of Treg was associated with high grades and a reduced overall survival. Treg were almost absent in endometrium tissues from healthy control patients. Co-culture of tumor cells with CD4 + CD25 + CD127dim Treg led to functional changes: enhanced invasion, migration and viability indicated that increased levels of Treg in the tumor microenvironment may promote tumor growth. Furthermore, we found that the presence of EC cells led to phenotypic changes in PBMC, showing significantly increased levels of CD25 and FoxP3. Conclusion Our results indicate that the presence of Treg in the EC tumor environment is associated with a poorer outcome. A remarkable impact of Treg on tumor cell behaviour and vice versa of tumor cells on PBMC subpopulations support this notion mechanistically. Our findings provide a basis for focusing on Treg as potential future therapeutic targets in EC. Endometrial cancer (dpeaa)DE-He213 Regulatory T-cells (dpeaa)DE-He213 FoxP3 (dpeaa)DE-He213 Immune escape (dpeaa)DE-He213 Survival (dpeaa)DE-He213 Mannewitz, Mareike aut Perleberg, Carolin aut Schnell, Konstantin aut Anz, David aut Hahn, Laura aut Meister, Sarah aut Schmoeckel, Elisa aut Burges, Alexander aut Czogalla, Bastian aut Hester, Anna aut Mahner, Sven aut Kessler, Mirjana aut Jeschke, Udo aut Corradini, Stefanie aut Trillsch, Fabian aut Beyer, Susanne aut Enthalten in Cellular oncology Amsterdam [u.a.] : IOS Press, 2004 45(2022), 6 vom: 13. Sept., Seite 1171-1185 (DE-627)392964430 (DE-600)2158254-3 1875-8606 nnns volume:45 year:2022 number:6 day:13 month:09 pages:1171-1185 https://dx.doi.org/10.1007/s13402-022-00708-2 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_702 AR 45 2022 6 13 09 1171-1185 |
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10.1007/s13402-022-00708-2 doi (DE-627)SPR048871311 (SPR)s13402-022-00708-2-e DE-627 ger DE-627 rakwb eng Kolben, Thomas verfasserin aut Presence of regulatory T-cells in endometrial cancer predicts poorer overall survival and promotes progression of tumor cells 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s) 2022 Purpose Endometrial cancer (EC) is one of the most common gynaecologic malignancies. Tumor infiltrating regulatory T-cells (Treg) have been reported to have a prognostic impact in many malignancies. Immunotherapeutic strategies are gaining interest for advanced and recurrent EC cases, where treatment options are rare. Our study was aimed at determining the value of Treg in EC progression. Methods EC specimens from 275 patients and 28 controls were screened immunohistochemically for the presence of Treg represented by FoxP3. Correlations with clinicopathological and survival parameters were performed. Functional assays were performed using EC cell lines Ishikawa + and RL95-2 after co-culturing with isolated CD4 + CD25 + CD127dim Treg. To assess the influence of EC on the composition of peripheral blood mononuclear cells (PBMC), flow cytometric analyses were performed. Results We found that an increased infiltration of Treg was associated with high grades and a reduced overall survival. Treg were almost absent in endometrium tissues from healthy control patients. Co-culture of tumor cells with CD4 + CD25 + CD127dim Treg led to functional changes: enhanced invasion, migration and viability indicated that increased levels of Treg in the tumor microenvironment may promote tumor growth. Furthermore, we found that the presence of EC cells led to phenotypic changes in PBMC, showing significantly increased levels of CD25 and FoxP3. Conclusion Our results indicate that the presence of Treg in the EC tumor environment is associated with a poorer outcome. A remarkable impact of Treg on tumor cell behaviour and vice versa of tumor cells on PBMC subpopulations support this notion mechanistically. Our findings provide a basis for focusing on Treg as potential future therapeutic targets in EC. Endometrial cancer (dpeaa)DE-He213 Regulatory T-cells (dpeaa)DE-He213 FoxP3 (dpeaa)DE-He213 Immune escape (dpeaa)DE-He213 Survival (dpeaa)DE-He213 Mannewitz, Mareike aut Perleberg, Carolin aut Schnell, Konstantin aut Anz, David aut Hahn, Laura aut Meister, Sarah aut Schmoeckel, Elisa aut Burges, Alexander aut Czogalla, Bastian aut Hester, Anna aut Mahner, Sven aut Kessler, Mirjana aut Jeschke, Udo aut Corradini, Stefanie aut Trillsch, Fabian aut Beyer, Susanne aut Enthalten in Cellular oncology Amsterdam [u.a.] : IOS Press, 2004 45(2022), 6 vom: 13. Sept., Seite 1171-1185 (DE-627)392964430 (DE-600)2158254-3 1875-8606 nnns volume:45 year:2022 number:6 day:13 month:09 pages:1171-1185 https://dx.doi.org/10.1007/s13402-022-00708-2 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_702 AR 45 2022 6 13 09 1171-1185 |
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10.1007/s13402-022-00708-2 doi (DE-627)SPR048871311 (SPR)s13402-022-00708-2-e DE-627 ger DE-627 rakwb eng Kolben, Thomas verfasserin aut Presence of regulatory T-cells in endometrial cancer predicts poorer overall survival and promotes progression of tumor cells 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s) 2022 Purpose Endometrial cancer (EC) is one of the most common gynaecologic malignancies. Tumor infiltrating regulatory T-cells (Treg) have been reported to have a prognostic impact in many malignancies. Immunotherapeutic strategies are gaining interest for advanced and recurrent EC cases, where treatment options are rare. Our study was aimed at determining the value of Treg in EC progression. Methods EC specimens from 275 patients and 28 controls were screened immunohistochemically for the presence of Treg represented by FoxP3. Correlations with clinicopathological and survival parameters were performed. Functional assays were performed using EC cell lines Ishikawa + and RL95-2 after co-culturing with isolated CD4 + CD25 + CD127dim Treg. To assess the influence of EC on the composition of peripheral blood mononuclear cells (PBMC), flow cytometric analyses were performed. Results We found that an increased infiltration of Treg was associated with high grades and a reduced overall survival. Treg were almost absent in endometrium tissues from healthy control patients. Co-culture of tumor cells with CD4 + CD25 + CD127dim Treg led to functional changes: enhanced invasion, migration and viability indicated that increased levels of Treg in the tumor microenvironment may promote tumor growth. Furthermore, we found that the presence of EC cells led to phenotypic changes in PBMC, showing significantly increased levels of CD25 and FoxP3. Conclusion Our results indicate that the presence of Treg in the EC tumor environment is associated with a poorer outcome. A remarkable impact of Treg on tumor cell behaviour and vice versa of tumor cells on PBMC subpopulations support this notion mechanistically. Our findings provide a basis for focusing on Treg as potential future therapeutic targets in EC. Endometrial cancer (dpeaa)DE-He213 Regulatory T-cells (dpeaa)DE-He213 FoxP3 (dpeaa)DE-He213 Immune escape (dpeaa)DE-He213 Survival (dpeaa)DE-He213 Mannewitz, Mareike aut Perleberg, Carolin aut Schnell, Konstantin aut Anz, David aut Hahn, Laura aut Meister, Sarah aut Schmoeckel, Elisa aut Burges, Alexander aut Czogalla, Bastian aut Hester, Anna aut Mahner, Sven aut Kessler, Mirjana aut Jeschke, Udo aut Corradini, Stefanie aut Trillsch, Fabian aut Beyer, Susanne aut Enthalten in Cellular oncology Amsterdam [u.a.] : IOS Press, 2004 45(2022), 6 vom: 13. Sept., Seite 1171-1185 (DE-627)392964430 (DE-600)2158254-3 1875-8606 nnns volume:45 year:2022 number:6 day:13 month:09 pages:1171-1185 https://dx.doi.org/10.1007/s13402-022-00708-2 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_702 AR 45 2022 6 13 09 1171-1185 |
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10.1007/s13402-022-00708-2 doi (DE-627)SPR048871311 (SPR)s13402-022-00708-2-e DE-627 ger DE-627 rakwb eng Kolben, Thomas verfasserin aut Presence of regulatory T-cells in endometrial cancer predicts poorer overall survival and promotes progression of tumor cells 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s) 2022 Purpose Endometrial cancer (EC) is one of the most common gynaecologic malignancies. Tumor infiltrating regulatory T-cells (Treg) have been reported to have a prognostic impact in many malignancies. Immunotherapeutic strategies are gaining interest for advanced and recurrent EC cases, where treatment options are rare. Our study was aimed at determining the value of Treg in EC progression. Methods EC specimens from 275 patients and 28 controls were screened immunohistochemically for the presence of Treg represented by FoxP3. Correlations with clinicopathological and survival parameters were performed. Functional assays were performed using EC cell lines Ishikawa + and RL95-2 after co-culturing with isolated CD4 + CD25 + CD127dim Treg. To assess the influence of EC on the composition of peripheral blood mononuclear cells (PBMC), flow cytometric analyses were performed. Results We found that an increased infiltration of Treg was associated with high grades and a reduced overall survival. Treg were almost absent in endometrium tissues from healthy control patients. Co-culture of tumor cells with CD4 + CD25 + CD127dim Treg led to functional changes: enhanced invasion, migration and viability indicated that increased levels of Treg in the tumor microenvironment may promote tumor growth. Furthermore, we found that the presence of EC cells led to phenotypic changes in PBMC, showing significantly increased levels of CD25 and FoxP3. Conclusion Our results indicate that the presence of Treg in the EC tumor environment is associated with a poorer outcome. A remarkable impact of Treg on tumor cell behaviour and vice versa of tumor cells on PBMC subpopulations support this notion mechanistically. Our findings provide a basis for focusing on Treg as potential future therapeutic targets in EC. Endometrial cancer (dpeaa)DE-He213 Regulatory T-cells (dpeaa)DE-He213 FoxP3 (dpeaa)DE-He213 Immune escape (dpeaa)DE-He213 Survival (dpeaa)DE-He213 Mannewitz, Mareike aut Perleberg, Carolin aut Schnell, Konstantin aut Anz, David aut Hahn, Laura aut Meister, Sarah aut Schmoeckel, Elisa aut Burges, Alexander aut Czogalla, Bastian aut Hester, Anna aut Mahner, Sven aut Kessler, Mirjana aut Jeschke, Udo aut Corradini, Stefanie aut Trillsch, Fabian aut Beyer, Susanne aut Enthalten in Cellular oncology Amsterdam [u.a.] : IOS Press, 2004 45(2022), 6 vom: 13. Sept., Seite 1171-1185 (DE-627)392964430 (DE-600)2158254-3 1875-8606 nnns volume:45 year:2022 number:6 day:13 month:09 pages:1171-1185 https://dx.doi.org/10.1007/s13402-022-00708-2 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_702 AR 45 2022 6 13 09 1171-1185 |
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Enthalten in Cellular oncology 45(2022), 6 vom: 13. Sept., Seite 1171-1185 volume:45 year:2022 number:6 day:13 month:09 pages:1171-1185 |
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Kolben, Thomas |
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Presence of regulatory T-cells in endometrial cancer predicts poorer overall survival and promotes progression of tumor cells Endometrial cancer (dpeaa)DE-He213 Regulatory T-cells (dpeaa)DE-He213 FoxP3 (dpeaa)DE-He213 Immune escape (dpeaa)DE-He213 Survival (dpeaa)DE-He213 |
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Presence of regulatory T-cells in endometrial cancer predicts poorer overall survival and promotes progression of tumor cells |
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Kolben, Thomas Mannewitz, Mareike Perleberg, Carolin Schnell, Konstantin Anz, David Hahn, Laura Meister, Sarah Schmoeckel, Elisa Burges, Alexander Czogalla, Bastian Hester, Anna Mahner, Sven Kessler, Mirjana Jeschke, Udo Corradini, Stefanie Trillsch, Fabian Beyer, Susanne |
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presence of regulatory t-cells in endometrial cancer predicts poorer overall survival and promotes progression of tumor cells |
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Presence of regulatory T-cells in endometrial cancer predicts poorer overall survival and promotes progression of tumor cells |
| abstract |
Purpose Endometrial cancer (EC) is one of the most common gynaecologic malignancies. Tumor infiltrating regulatory T-cells (Treg) have been reported to have a prognostic impact in many malignancies. Immunotherapeutic strategies are gaining interest for advanced and recurrent EC cases, where treatment options are rare. Our study was aimed at determining the value of Treg in EC progression. Methods EC specimens from 275 patients and 28 controls were screened immunohistochemically for the presence of Treg represented by FoxP3. Correlations with clinicopathological and survival parameters were performed. Functional assays were performed using EC cell lines Ishikawa + and RL95-2 after co-culturing with isolated CD4 + CD25 + CD127dim Treg. To assess the influence of EC on the composition of peripheral blood mononuclear cells (PBMC), flow cytometric analyses were performed. Results We found that an increased infiltration of Treg was associated with high grades and a reduced overall survival. Treg were almost absent in endometrium tissues from healthy control patients. Co-culture of tumor cells with CD4 + CD25 + CD127dim Treg led to functional changes: enhanced invasion, migration and viability indicated that increased levels of Treg in the tumor microenvironment may promote tumor growth. Furthermore, we found that the presence of EC cells led to phenotypic changes in PBMC, showing significantly increased levels of CD25 and FoxP3. Conclusion Our results indicate that the presence of Treg in the EC tumor environment is associated with a poorer outcome. A remarkable impact of Treg on tumor cell behaviour and vice versa of tumor cells on PBMC subpopulations support this notion mechanistically. Our findings provide a basis for focusing on Treg as potential future therapeutic targets in EC. © The Author(s) 2022 |
| abstractGer |
Purpose Endometrial cancer (EC) is one of the most common gynaecologic malignancies. Tumor infiltrating regulatory T-cells (Treg) have been reported to have a prognostic impact in many malignancies. Immunotherapeutic strategies are gaining interest for advanced and recurrent EC cases, where treatment options are rare. Our study was aimed at determining the value of Treg in EC progression. Methods EC specimens from 275 patients and 28 controls were screened immunohistochemically for the presence of Treg represented by FoxP3. Correlations with clinicopathological and survival parameters were performed. Functional assays were performed using EC cell lines Ishikawa + and RL95-2 after co-culturing with isolated CD4 + CD25 + CD127dim Treg. To assess the influence of EC on the composition of peripheral blood mononuclear cells (PBMC), flow cytometric analyses were performed. Results We found that an increased infiltration of Treg was associated with high grades and a reduced overall survival. Treg were almost absent in endometrium tissues from healthy control patients. Co-culture of tumor cells with CD4 + CD25 + CD127dim Treg led to functional changes: enhanced invasion, migration and viability indicated that increased levels of Treg in the tumor microenvironment may promote tumor growth. Furthermore, we found that the presence of EC cells led to phenotypic changes in PBMC, showing significantly increased levels of CD25 and FoxP3. Conclusion Our results indicate that the presence of Treg in the EC tumor environment is associated with a poorer outcome. A remarkable impact of Treg on tumor cell behaviour and vice versa of tumor cells on PBMC subpopulations support this notion mechanistically. Our findings provide a basis for focusing on Treg as potential future therapeutic targets in EC. © The Author(s) 2022 |
| abstract_unstemmed |
Purpose Endometrial cancer (EC) is one of the most common gynaecologic malignancies. Tumor infiltrating regulatory T-cells (Treg) have been reported to have a prognostic impact in many malignancies. Immunotherapeutic strategies are gaining interest for advanced and recurrent EC cases, where treatment options are rare. Our study was aimed at determining the value of Treg in EC progression. Methods EC specimens from 275 patients and 28 controls were screened immunohistochemically for the presence of Treg represented by FoxP3. Correlations with clinicopathological and survival parameters were performed. Functional assays were performed using EC cell lines Ishikawa + and RL95-2 after co-culturing with isolated CD4 + CD25 + CD127dim Treg. To assess the influence of EC on the composition of peripheral blood mononuclear cells (PBMC), flow cytometric analyses were performed. Results We found that an increased infiltration of Treg was associated with high grades and a reduced overall survival. Treg were almost absent in endometrium tissues from healthy control patients. Co-culture of tumor cells with CD4 + CD25 + CD127dim Treg led to functional changes: enhanced invasion, migration and viability indicated that increased levels of Treg in the tumor microenvironment may promote tumor growth. Furthermore, we found that the presence of EC cells led to phenotypic changes in PBMC, showing significantly increased levels of CD25 and FoxP3. Conclusion Our results indicate that the presence of Treg in the EC tumor environment is associated with a poorer outcome. A remarkable impact of Treg on tumor cell behaviour and vice versa of tumor cells on PBMC subpopulations support this notion mechanistically. Our findings provide a basis for focusing on Treg as potential future therapeutic targets in EC. © The Author(s) 2022 |
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Presence of regulatory T-cells in endometrial cancer predicts poorer overall survival and promotes progression of tumor cells |
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Tumor infiltrating regulatory T-cells (Treg) have been reported to have a prognostic impact in many malignancies. Immunotherapeutic strategies are gaining interest for advanced and recurrent EC cases, where treatment options are rare. Our study was aimed at determining the value of Treg in EC progression. Methods EC specimens from 275 patients and 28 controls were screened immunohistochemically for the presence of Treg represented by FoxP3. Correlations with clinicopathological and survival parameters were performed. Functional assays were performed using EC cell lines Ishikawa + and RL95-2 after co-culturing with isolated CD4 + CD25 + CD127dim Treg. To assess the influence of EC on the composition of peripheral blood mononuclear cells (PBMC), flow cytometric analyses were performed. Results We found that an increased infiltration of Treg was associated with high grades and a reduced overall survival. Treg were almost absent in endometrium tissues from healthy control patients. Co-culture of tumor cells with CD4 + CD25 + CD127dim Treg led to functional changes: enhanced invasion, migration and viability indicated that increased levels of Treg in the tumor microenvironment may promote tumor growth. Furthermore, we found that the presence of EC cells led to phenotypic changes in PBMC, showing significantly increased levels of CD25 and FoxP3. Conclusion Our results indicate that the presence of Treg in the EC tumor environment is associated with a poorer outcome. A remarkable impact of Treg on tumor cell behaviour and vice versa of tumor cells on PBMC subpopulations support this notion mechanistically. 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