Monocyte Maturation Mediators Upregulate CD83, ICAM-1 and MHC Class 1 Expression on Ewing’s Sarcoma, Enhancing T Cell Cytotoxicity
| Autor: | Uwe Thiel, Emilie Biele, Kristina von Heyking, Melanie Thiede, Stefan Burdach, Carolin Prexler, Sebastian J. Schober, Jennifer Eck, Busheng Xue, Hendrik Gassmann |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
QH301-705.5
medicine.medical_treatment T cell Cell Immunoglobulins Sarcoma Ewing Monocytes Article Antigens CD CD83 Cell Line Tumor MHC class I medicine Cytotoxic T cell Humans Biology (General) Tumor microenvironment Membrane Glycoproteins biology business.industry Tumor Necrosis Factor-alpha Histocompatibility Antigens Class I Ewing's sarcoma General Medicine Immunotherapy Dendritic Cells CHM1319-specific TCR-transgenic T cells medicine.disease Intercellular Adhesion Molecule-1 Up-Regulation Gene Expression Regulation Neoplastic medicine.anatomical_structure Cancer research biology.protein Tumor necrosis factor alpha immunotherapy business Ewing sarcoma T-Lymphocytes Cytotoxic |
| Zdroj: | Cells Volume 10 Issue 11 Cells, Vol 10, Iss 3070, p 3070 (2021) |
| ISSN: | 2073-4409 |
| DOI: | 10.3390/cells10113070 |
| Popis: | 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 CHM1319-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 CHM1319-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 CHM1319-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 PGE2 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 CHM1319/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. |
| Databáze: | OpenAIRE |
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