Monocyte Maturation Mediators Upregulate CD83, ICAM-1 and MHC Class 1 Expression on Ewing’s Sarcoma, Enhancing T Cell Cytotoxicity
Ewing’s sarcoma (EwS) is a pediatric solid tumor entity with low somatic mutational burden and a low rate of tumor-infiltrating T cells, indicating a low extent of immunogenicity. In EwS, immunogenicity may furthermore be significantly diminished by a predominantly M2 macrophage driven pro-tumorigen...
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MDPI AG
2021-11-01
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| author | Emilie Biele Sebastian J. Schober Carolin Prexler Melanie Thiede Kristina von Heyking Hendrik Gassmann Jennifer Eck Busheng Xue Stefan Burdach Uwe Thiel |
| author_facet | Emilie Biele Sebastian J. Schober Carolin Prexler Melanie Thiede Kristina von Heyking Hendrik Gassmann Jennifer Eck Busheng Xue Stefan Burdach Uwe Thiel |
| author_sort | Emilie Biele |
| collection | DOAJ |
| description | Ewing’s sarcoma (EwS) is a pediatric solid tumor entity with low somatic mutational burden and a low rate of tumor-infiltrating T cells, indicating a low extent of immunogenicity. In EwS, immunogenicity may furthermore be significantly diminished by a predominantly M2 macrophage driven pro-tumorigenic tumor microenvironment. In the past, we demonstrated that CHM1<sup>319</sup>-specific TCR-transgenic T cells are able to control EwS growth in a preclinical mouse model as well as in a patient with metastatic disease. However, new adjuvant techniques to induce long lasting and curative CHM1<sup>319</sup>-specific TCR-transgenic T cell-mediated anti-tumor responses are needed. In this work, we sought to identify a technique to improve the cytotoxic effect of CHM1<sup>319</sup>-specific TCR-transgenic T cell by altering the immunogenic cell surface marker expression on EwS cell lines using different cytokines. We demonstrate that TNF, IL-6, IL-1β and PGE<sub>2</sub> cause pro-immunogenic CD83, MHC class I and II as well as ICAM-1 upregulation in EwS cell lines. This observation was associated with significantly improved recognition and killing of the tumor cells by EwS-specific CHM1<sup>319</sup>/HLA-A*02:01-restricted TCR-transgenic T cells. Conclusively, we demonstrate that the induction of an inflammatory signature renders EwS more susceptible to adoptive T cell therapy. TNF, which is upregulated during inflammatory processes, is of particular translational interest as its secretion may be induced in the patients e.g., by irradiation and hyperthermia in the clinical setting. In future clinical protocols, this finding may be important to identify appropriate conditioning regimens as well as point of time for adoptive T cell-based immunotherapy in EwS patients. |
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| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-10T05:36:33Z |
| publishDate | 2021-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-a017ee78320743c3be409bf39ee9343b2023-11-22T22:50:53ZengMDPI AGCells2073-44092021-11-011011307010.3390/cells10113070Monocyte Maturation Mediators Upregulate CD83, ICAM-1 and MHC Class 1 Expression on Ewing’s Sarcoma, Enhancing T Cell CytotoxicityEmilie Biele0Sebastian J. Schober1Carolin Prexler2Melanie Thiede3Kristina von Heyking4Hendrik Gassmann5Jennifer Eck6Busheng Xue7Stefan Burdach8Uwe Thiel9Department of Pediatrics, Children’s Cancer Research Center, Kinderklinik München Schwabing, School of Medicine, Technical University of Munich, 80804 Munich, GermanyDepartment of Pediatrics, Children’s Cancer Research Center, Kinderklinik München Schwabing, School of Medicine, Technical University of Munich, 80804 Munich, GermanyDepartment of Pediatrics, Children’s Cancer Research Center, Kinderklinik München Schwabing, School of Medicine, Technical University of Munich, 80804 Munich, GermanyDepartment of Pediatrics, Children’s Cancer Research Center, Kinderklinik München Schwabing, School of Medicine, Technical University of Munich, 80804 Munich, GermanyDepartment of Pediatrics, Children’s Cancer Research Center, Kinderklinik München Schwabing, School of Medicine, Technical University of Munich, 80804 Munich, GermanyDepartment of Pediatrics, Children’s Cancer Research Center, Kinderklinik München Schwabing, School of Medicine, Technical University of Munich, 80804 Munich, GermanyDepartment of Pediatrics, Children’s Cancer Research Center, Kinderklinik München Schwabing, School of Medicine, Technical University of Munich, 80804 Munich, GermanyDepartment of Pediatrics, Children’s Cancer Research Center, Kinderklinik München Schwabing, School of Medicine, Technical University of Munich, 80804 Munich, GermanyDepartment of Pediatrics, Children’s Cancer Research Center, Kinderklinik München Schwabing, School of Medicine, Technical University of Munich, 80804 Munich, GermanyDepartment of Pediatrics, Children’s Cancer Research Center, Kinderklinik München Schwabing, School of Medicine, Technical University of Munich, 80804 Munich, GermanyEwing’s sarcoma (EwS) is a pediatric solid tumor entity with low somatic mutational burden and a low rate of tumor-infiltrating T cells, indicating a low extent of immunogenicity. In EwS, immunogenicity may furthermore be significantly diminished by a predominantly M2 macrophage driven pro-tumorigenic tumor microenvironment. In the past, we demonstrated that CHM1<sup>319</sup>-specific TCR-transgenic T cells are able to control EwS growth in a preclinical mouse model as well as in a patient with metastatic disease. However, new adjuvant techniques to induce long lasting and curative CHM1<sup>319</sup>-specific TCR-transgenic T cell-mediated anti-tumor responses are needed. In this work, we sought to identify a technique to improve the cytotoxic effect of CHM1<sup>319</sup>-specific TCR-transgenic T cell by altering the immunogenic cell surface marker expression on EwS cell lines using different cytokines. We demonstrate that TNF, IL-6, IL-1β and PGE<sub>2</sub> cause pro-immunogenic CD83, MHC class I and II as well as ICAM-1 upregulation in EwS cell lines. This observation was associated with significantly improved recognition and killing of the tumor cells by EwS-specific CHM1<sup>319</sup>/HLA-A*02:01-restricted TCR-transgenic T cells. Conclusively, we demonstrate that the induction of an inflammatory signature renders EwS more susceptible to adoptive T cell therapy. TNF, which is upregulated during inflammatory processes, is of particular translational interest as its secretion may be induced in the patients e.g., by irradiation and hyperthermia in the clinical setting. In future clinical protocols, this finding may be important to identify appropriate conditioning regimens as well as point of time for adoptive T cell-based immunotherapy in EwS patients.https://www.mdpi.com/2073-4409/10/11/3070Ewing sarcomaCD83immunotherapyCHM1<sup>319</sup>-specific TCR-transgenic T cells |
| spellingShingle | Emilie Biele Sebastian J. Schober Carolin Prexler Melanie Thiede Kristina von Heyking Hendrik Gassmann Jennifer Eck Busheng Xue Stefan Burdach Uwe Thiel Monocyte Maturation Mediators Upregulate CD83, ICAM-1 and MHC Class 1 Expression on Ewing’s Sarcoma, Enhancing T Cell Cytotoxicity Cells Ewing sarcoma CD83 immunotherapy CHM1<sup>319</sup>-specific TCR-transgenic T cells |
| title | Monocyte Maturation Mediators Upregulate CD83, ICAM-1 and MHC Class 1 Expression on Ewing’s Sarcoma, Enhancing T Cell Cytotoxicity |
| title_full | Monocyte Maturation Mediators Upregulate CD83, ICAM-1 and MHC Class 1 Expression on Ewing’s Sarcoma, Enhancing T Cell Cytotoxicity |
| title_fullStr | Monocyte Maturation Mediators Upregulate CD83, ICAM-1 and MHC Class 1 Expression on Ewing’s Sarcoma, Enhancing T Cell Cytotoxicity |
| title_full_unstemmed | Monocyte Maturation Mediators Upregulate CD83, ICAM-1 and MHC Class 1 Expression on Ewing’s Sarcoma, Enhancing T Cell Cytotoxicity |
| title_short | Monocyte Maturation Mediators Upregulate CD83, ICAM-1 and MHC Class 1 Expression on Ewing’s Sarcoma, Enhancing T Cell Cytotoxicity |
| title_sort | monocyte maturation mediators upregulate cd83 icam 1 and mhc class 1 expression on ewing s sarcoma enhancing t cell cytotoxicity |
| topic | Ewing sarcoma CD83 immunotherapy CHM1<sup>319</sup>-specific TCR-transgenic T cells |
| url | https://www.mdpi.com/2073-4409/10/11/3070 |
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