Clinical implications of systemic and local immune responses in human angiosarcoma

Abstract Angiosarcomas are a rare subtype of soft-tissue sarcomas which exhibit aggressive clinical phenotypes with limited treatment options and poor outcomes. In this study, we investigated the clinical relevance of the peripheral blood neutrophil-to-lymphocyte ratio (NLR) as a marker of systemic...

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Autores principales:	Jason Yongsheng Chan, Grace Fangmin Tan, Joe Yeong, Chee Wee Ong, Dave Yong Xiang Ng, Elizabeth Lee, Joanna Koh, Cedric Chuan-Young Ng, Jing Yi Lee, Wei Liu, Ru Xin Wong, Chin-Ann Johnny Ong, Mohamad Farid, Bin Tean Teh, Khee Chee Soo
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
Acceso en línea:	https://doaj.org/article/5d397cd279614abe8c61f05978d8c078
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spelling	oai:doaj.org-article:5d397cd279614abe8c61f05978d8c0782021-12-02T16:06:10ZClinical implications of systemic and local immune responses in human angiosarcoma10.1038/s41698-021-00150-x2397-768Xhttps://doaj.org/article/5d397cd279614abe8c61f05978d8c0782021-02-01T00:00:00Zhttps://doi.org/10.1038/s41698-021-00150-xhttps://doaj.org/toc/2397-768XAbstract Angiosarcomas are a rare subtype of soft-tissue sarcomas which exhibit aggressive clinical phenotypes with limited treatment options and poor outcomes. In this study, we investigated the clinical relevance of the peripheral blood neutrophil-to-lymphocyte ratio (NLR) as a marker of systemic immune response, as well as its correlation with intra-tumoral immune profiles in a subgroup of cases (n = 35) using the NanoString PanCancer IO360 panel and multiplex immunohistochemistry. In the overall cohort (n = 150), angiosarcomas of the head and neck (AS-HN) comprised most cases (58.7%) and median overall survival (OS) was 1.1 year. NLR, classified as high in 78 of 112 (70%) evaluable patients, was independently correlated with worse OS (HR 1.84, 95%CI 1.18–2.87, p = 0.0073). Peripheral blood NLR was positively correlated with intra-tumoral NLR (tNLR) (Spearman’s rho 0.450, p = 0.0067). Visualization of tumor-infiltrating immune cells confirmed that tNLR scores correlated directly with both neutrophil (CD15+ cells, rho 0.398, p = 0.0198) and macrophage (CD68+ cells, rho 0.515, p = 0.0018) cell counts. Interestingly, tNLR correlated positively with oncogenic pathway scores including angiogenesis, matrix remodeling and metastasis, and cytokine and chemokine signaling, as well as myeloid compartment scores (all p < 0.001). In patients with documented response assessment to first-line chemotherapy, these pathway scores were all significantly higher in non-responders (47%) compared to responders. In conclusion, systemic and local immune responses may inform chemotherapy response and clinical outcomes in angiosarcomas.Jason Yongsheng ChanGrace Fangmin TanJoe YeongChee Wee OngDave Yong Xiang NgElizabeth LeeJoanna KohCedric Chuan-Young NgJing Yi LeeWei LiuRu Xin WongChin-Ann Johnny OngMohamad FaridBin Tean TehKhee Chee SooNature PortfolioarticleNeoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENnpj Precision Oncology, Vol 5, Iss 1, Pp 1-13 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
spellingShingle	Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Jason Yongsheng Chan Grace Fangmin Tan Joe Yeong Chee Wee Ong Dave Yong Xiang Ng Elizabeth Lee Joanna Koh Cedric Chuan-Young Ng Jing Yi Lee Wei Liu Ru Xin Wong Chin-Ann Johnny Ong Mohamad Farid Bin Tean Teh Khee Chee Soo Clinical implications of systemic and local immune responses in human angiosarcoma
description	Abstract Angiosarcomas are a rare subtype of soft-tissue sarcomas which exhibit aggressive clinical phenotypes with limited treatment options and poor outcomes. In this study, we investigated the clinical relevance of the peripheral blood neutrophil-to-lymphocyte ratio (NLR) as a marker of systemic immune response, as well as its correlation with intra-tumoral immune profiles in a subgroup of cases (n = 35) using the NanoString PanCancer IO360 panel and multiplex immunohistochemistry. In the overall cohort (n = 150), angiosarcomas of the head and neck (AS-HN) comprised most cases (58.7%) and median overall survival (OS) was 1.1 year. NLR, classified as high in 78 of 112 (70%) evaluable patients, was independently correlated with worse OS (HR 1.84, 95%CI 1.18–2.87, p = 0.0073). Peripheral blood NLR was positively correlated with intra-tumoral NLR (tNLR) (Spearman’s rho 0.450, p = 0.0067). Visualization of tumor-infiltrating immune cells confirmed that tNLR scores correlated directly with both neutrophil (CD15+ cells, rho 0.398, p = 0.0198) and macrophage (CD68+ cells, rho 0.515, p = 0.0018) cell counts. Interestingly, tNLR correlated positively with oncogenic pathway scores including angiogenesis, matrix remodeling and metastasis, and cytokine and chemokine signaling, as well as myeloid compartment scores (all p < 0.001). In patients with documented response assessment to first-line chemotherapy, these pathway scores were all significantly higher in non-responders (47%) compared to responders. In conclusion, systemic and local immune responses may inform chemotherapy response and clinical outcomes in angiosarcomas.
format	article
author	Jason Yongsheng Chan Grace Fangmin Tan Joe Yeong Chee Wee Ong Dave Yong Xiang Ng Elizabeth Lee Joanna Koh Cedric Chuan-Young Ng Jing Yi Lee Wei Liu Ru Xin Wong Chin-Ann Johnny Ong Mohamad Farid Bin Tean Teh Khee Chee Soo
author_facet	Jason Yongsheng Chan Grace Fangmin Tan Joe Yeong Chee Wee Ong Dave Yong Xiang Ng Elizabeth Lee Joanna Koh Cedric Chuan-Young Ng Jing Yi Lee Wei Liu Ru Xin Wong Chin-Ann Johnny Ong Mohamad Farid Bin Tean Teh Khee Chee Soo
author_sort	Jason Yongsheng Chan
title	Clinical implications of systemic and local immune responses in human angiosarcoma
title_short	Clinical implications of systemic and local immune responses in human angiosarcoma
title_full	Clinical implications of systemic and local immune responses in human angiosarcoma
title_fullStr	Clinical implications of systemic and local immune responses in human angiosarcoma
title_full_unstemmed	Clinical implications of systemic and local immune responses in human angiosarcoma
title_sort	clinical implications of systemic and local immune responses in human angiosarcoma
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/5d397cd279614abe8c61f05978d8c078
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Clinical implications of systemic and local immune responses in human angiosarcoma

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