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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Autores principales:	Emilie Biele, Sebastian J. Schober, Carolin Prexler, Melanie Thiede, Kristina von Heyking, Hendrik Gassmann, Jennifer Eck, Busheng Xue, Stefan Burdach, Uwe Thiel
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	Ewing sarcoma CD83 immunotherapy CHM1<sup>319</sup>-specific TCR-transgenic T cells Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/a017ee78320743c3be409bf39ee9343b
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spelling	oai:doaj.org-article:a017ee78320743c3be409bf39ee9343b2021-11-25T17:11:11ZMonocyte Maturation Mediators Upregulate CD83, ICAM-1 and MHC Class 1 Expression on Ewing’s Sarcoma, Enhancing T Cell Cytotoxicity10.3390/cells101130702073-4409https://doaj.org/article/a017ee78320743c3be409bf39ee9343b2021-11-01T00:00:00Zhttps://www.mdpi.com/2073-4409/10/11/3070https://doaj.org/toc/2073-4409Ewing’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.Emilie BieleSebastian J. SchoberCarolin PrexlerMelanie ThiedeKristina von HeykingHendrik GassmannJennifer EckBusheng XueStefan BurdachUwe ThielMDPI AGarticleEwing sarcomaCD83immunotherapyCHM1<sup>319</sup>-specific TCR-transgenic T cellsBiology (General)QH301-705.5ENCells, Vol 10, Iss 3070, p 3070 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Ewing sarcoma CD83 immunotherapy CHM1<sup>319</sup>-specific TCR-transgenic T cells Biology (General) QH301-705.5
spellingShingle	Ewing sarcoma CD83 immunotherapy CHM1<sup>319</sup>-specific TCR-transgenic T cells Biology (General) QH301-705.5 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
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.
format	article
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
title	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_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_sort	monocyte maturation mediators upregulate cd83, icam-1 and mhc class 1 expression on ewing’s sarcoma, enhancing t cell cytotoxicity
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/a017ee78320743c3be409bf39ee9343b
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Monocyte Maturation Mediators Upregulate CD83, ICAM-1 and MHC Class 1 Expression on Ewing’s Sarcoma, Enhancing T Cell Cytotoxicity

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