Chemoradiation induces upregulation of immunogenic cell death-related molecules together with increased expression of PD-L1 and galectin-9 in gastric cancer

Abstract Surgery alone or combined with chemo- and/or radiation therapy remains the primary treatment for gastric cancer (GC) to date and immunotherapeutic tools such as monoclonal antibodies are only slowly being implemented. This is partly due to the fact that the immune microenvironment in GC dur...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	S. H. Petersen, L. F. Kua, S. Nakajima, W. P. Yong, K. Kono
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/2d376157ea7b4de7a0d8620adade5ed4
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:2d376157ea7b4de7a0d8620adade5ed4
record_format	dspace
spelling	oai:doaj.org-article:2d376157ea7b4de7a0d8620adade5ed42021-12-02T17:30:34ZChemoradiation induces upregulation of immunogenic cell death-related molecules together with increased expression of PD-L1 and galectin-9 in gastric cancer10.1038/s41598-021-91603-72045-2322https://doaj.org/article/2d376157ea7b4de7a0d8620adade5ed42021-06-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-91603-7https://doaj.org/toc/2045-2322Abstract Surgery alone or combined with chemo- and/or radiation therapy remains the primary treatment for gastric cancer (GC) to date and immunotherapeutic tools such as monoclonal antibodies are only slowly being implemented. This is partly due to the fact that the immune microenvironment in GC during chemoradiation and other treatment modalities is still poorly understood. 7 gastric cancer (GC) cell lines were tested for their response to chemoradiation using 5-FU in combination with X-ray irradiation. We conducted flow cytometric analysis to determine the cells’ ability to undergo immunogenic cell death (ICD) and their expression of the two immunosuppressive proteins programmed death-ligand 1 (PD-L1) and galectin-9 (Gal-9). We evaluated the overall immunogenicity of two cell lines (MKN7, MKN74) in co-culture experiments with human monocyte-derived dendritic cells (Mo-DCs). Chemoradiation induces distinct responses in different GC cell lines. We observe ICD in vitro in all tested GC cell lines in the form of calreticulin (CRT) translocation to the plasma membrane. As a resistance mechanism, these cells also upregulated Gal-9 and PD-L1. Mo-DC maturation experiments showed that GCs provoked the maturation of Mo-DCs after chemoradiation in vitro. The addition of α-PD-L1 blocking antibody further enhanced the immunogenicity of these cells while improving DC viability. Blocking Tim-3, as the main receptor for Gal-9, had no such effect. Our findings suggest that the benefits of chemoradiation can substantially depend on tumor subtype and these benefits can be offset by induced immune evasion in GC. Combination treatment using checkpoint inhibitors could potentially lead to enhanced immune responses and yield better patient outcomes.S. H. PetersenL. F. KuaS. NakajimaW. P. YongK. KonoNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q S. H. Petersen L. F. Kua S. Nakajima W. P. Yong K. Kono Chemoradiation induces upregulation of immunogenic cell death-related molecules together with increased expression of PD-L1 and galectin-9 in gastric cancer
description	Abstract Surgery alone or combined with chemo- and/or radiation therapy remains the primary treatment for gastric cancer (GC) to date and immunotherapeutic tools such as monoclonal antibodies are only slowly being implemented. This is partly due to the fact that the immune microenvironment in GC during chemoradiation and other treatment modalities is still poorly understood. 7 gastric cancer (GC) cell lines were tested for their response to chemoradiation using 5-FU in combination with X-ray irradiation. We conducted flow cytometric analysis to determine the cells’ ability to undergo immunogenic cell death (ICD) and their expression of the two immunosuppressive proteins programmed death-ligand 1 (PD-L1) and galectin-9 (Gal-9). We evaluated the overall immunogenicity of two cell lines (MKN7, MKN74) in co-culture experiments with human monocyte-derived dendritic cells (Mo-DCs). Chemoradiation induces distinct responses in different GC cell lines. We observe ICD in vitro in all tested GC cell lines in the form of calreticulin (CRT) translocation to the plasma membrane. As a resistance mechanism, these cells also upregulated Gal-9 and PD-L1. Mo-DC maturation experiments showed that GCs provoked the maturation of Mo-DCs after chemoradiation in vitro. The addition of α-PD-L1 blocking antibody further enhanced the immunogenicity of these cells while improving DC viability. Blocking Tim-3, as the main receptor for Gal-9, had no such effect. Our findings suggest that the benefits of chemoradiation can substantially depend on tumor subtype and these benefits can be offset by induced immune evasion in GC. Combination treatment using checkpoint inhibitors could potentially lead to enhanced immune responses and yield better patient outcomes.
format	article
author	S. H. Petersen L. F. Kua S. Nakajima W. P. Yong K. Kono
author_facet	S. H. Petersen L. F. Kua S. Nakajima W. P. Yong K. Kono
author_sort	S. H. Petersen
title	Chemoradiation induces upregulation of immunogenic cell death-related molecules together with increased expression of PD-L1 and galectin-9 in gastric cancer
title_short	Chemoradiation induces upregulation of immunogenic cell death-related molecules together with increased expression of PD-L1 and galectin-9 in gastric cancer
title_full	Chemoradiation induces upregulation of immunogenic cell death-related molecules together with increased expression of PD-L1 and galectin-9 in gastric cancer
title_fullStr	Chemoradiation induces upregulation of immunogenic cell death-related molecules together with increased expression of PD-L1 and galectin-9 in gastric cancer
title_full_unstemmed	Chemoradiation induces upregulation of immunogenic cell death-related molecules together with increased expression of PD-L1 and galectin-9 in gastric cancer
title_sort	chemoradiation induces upregulation of immunogenic cell death-related molecules together with increased expression of pd-l1 and galectin-9 in gastric cancer
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/2d376157ea7b4de7a0d8620adade5ed4
work_keys_str_mv	AT shpetersen chemoradiationinducesupregulationofimmunogeniccelldeathrelatedmoleculestogetherwithincreasedexpressionofpdl1andgalectin9ingastriccancer AT lfkua chemoradiationinducesupregulationofimmunogeniccelldeathrelatedmoleculestogetherwithincreasedexpressionofpdl1andgalectin9ingastriccancer AT snakajima chemoradiationinducesupregulationofimmunogeniccelldeathrelatedmoleculestogetherwithincreasedexpressionofpdl1andgalectin9ingastriccancer AT wpyong chemoradiationinducesupregulationofimmunogeniccelldeathrelatedmoleculestogetherwithincreasedexpressionofpdl1andgalectin9ingastriccancer AT kkono chemoradiationinducesupregulationofimmunogeniccelldeathrelatedmoleculestogetherwithincreasedexpressionofpdl1andgalectin9ingastriccancer
_version_	1718380721221926912

Chemoradiation induces upregulation of immunogenic cell death-related molecules together with increased expression of PD-L1 and galectin-9 in gastric cancer

Ejemplares similares