Multiplex immunohistochemistry accurately defines the immune context of metastatic melanoma

Abstract A prospective study explored the heterogeneous nature of metastatic melanoma using Multiplex immunohistochemistry (IHC) and flow cytometry (FACS). Multiplex IHC data quantitated immune subset number present intra-tumoral (IT) vs the tumor stroma, plus distance of immune subsets from the tum...

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Autores principales:	H. Halse, A. J. Colebatch, P. Petrone, M. A. Henderson, J. K. Mills, H. Snow, J. A. Westwood, S. Sandhu, J. M. Raleigh, A. Behren, J. Cebon, P. K. Darcy, M. H. Kershaw, G. A. McArthur, D. E. Gyorki, P. J. Neeson
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2018
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/1046ef03187a4802bf52b2ca77c01675
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spelling	oai:doaj.org-article:1046ef03187a4802bf52b2ca77c016752021-12-02T15:07:58ZMultiplex immunohistochemistry accurately defines the immune context of metastatic melanoma10.1038/s41598-018-28944-32045-2322https://doaj.org/article/1046ef03187a4802bf52b2ca77c016752018-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-018-28944-3https://doaj.org/toc/2045-2322Abstract A prospective study explored the heterogeneous nature of metastatic melanoma using Multiplex immunohistochemistry (IHC) and flow cytometry (FACS). Multiplex IHC data quantitated immune subset number present intra-tumoral (IT) vs the tumor stroma, plus distance of immune subsets from the tumor margin (TM). In addition, mIHC showed a close association between the presence of IT CD8+ T cells and PDL1 expression in melanoma, which was more prevalent on macrophages than on melanoma cells. In contrast, FACS provided more detailed information regarding the T cell subset differentiation, their activation status and expression of immune checkpoint molecules. Interestingly, mIHC detected significantly higher Treg numbers than FACS and showed preferential CD4+ T cell distribution in the tumor stroma. Based on the mIHC and FACS data, we provide a model which defines metastatic melanoma immune context into four categories using the presence or absence of PDL1+ melanoma cells and/or macrophages, and their location within the tumor or on the periphery, combined with the presence or absence of IT CD8+ T cells. This model interprets melanoma immune context as a spectrum of tumor escape from immune control, and provides a snapshot upon which interpretation of checkpoint blockade inhibitor (CBI) therapy responses can be built.H. HalseA. J. ColebatchP. PetroneM. A. HendersonJ. K. MillsH. SnowJ. A. WestwoodS. SandhuJ. M. RaleighA. BehrenJ. CebonP. K. DarcyM. H. KershawG. A. McArthurD. E. GyorkiP. J. NeesonNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 8, Iss 1, Pp 1-14 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q H. Halse A. J. Colebatch P. Petrone M. A. Henderson J. K. Mills H. Snow J. A. Westwood S. Sandhu J. M. Raleigh A. Behren J. Cebon P. K. Darcy M. H. Kershaw G. A. McArthur D. E. Gyorki P. J. Neeson Multiplex immunohistochemistry accurately defines the immune context of metastatic melanoma
description	Abstract A prospective study explored the heterogeneous nature of metastatic melanoma using Multiplex immunohistochemistry (IHC) and flow cytometry (FACS). Multiplex IHC data quantitated immune subset number present intra-tumoral (IT) vs the tumor stroma, plus distance of immune subsets from the tumor margin (TM). In addition, mIHC showed a close association between the presence of IT CD8+ T cells and PDL1 expression in melanoma, which was more prevalent on macrophages than on melanoma cells. In contrast, FACS provided more detailed information regarding the T cell subset differentiation, their activation status and expression of immune checkpoint molecules. Interestingly, mIHC detected significantly higher Treg numbers than FACS and showed preferential CD4+ T cell distribution in the tumor stroma. Based on the mIHC and FACS data, we provide a model which defines metastatic melanoma immune context into four categories using the presence or absence of PDL1+ melanoma cells and/or macrophages, and their location within the tumor or on the periphery, combined with the presence or absence of IT CD8+ T cells. This model interprets melanoma immune context as a spectrum of tumor escape from immune control, and provides a snapshot upon which interpretation of checkpoint blockade inhibitor (CBI) therapy responses can be built.
format	article
author	H. Halse A. J. Colebatch P. Petrone M. A. Henderson J. K. Mills H. Snow J. A. Westwood S. Sandhu J. M. Raleigh A. Behren J. Cebon P. K. Darcy M. H. Kershaw G. A. McArthur D. E. Gyorki P. J. Neeson
author_facet	H. Halse A. J. Colebatch P. Petrone M. A. Henderson J. K. Mills H. Snow J. A. Westwood S. Sandhu J. M. Raleigh A. Behren J. Cebon P. K. Darcy M. H. Kershaw G. A. McArthur D. E. Gyorki P. J. Neeson
author_sort	H. Halse
title	Multiplex immunohistochemistry accurately defines the immune context of metastatic melanoma
title_short	Multiplex immunohistochemistry accurately defines the immune context of metastatic melanoma
title_full	Multiplex immunohistochemistry accurately defines the immune context of metastatic melanoma
title_fullStr	Multiplex immunohistochemistry accurately defines the immune context of metastatic melanoma
title_full_unstemmed	Multiplex immunohistochemistry accurately defines the immune context of metastatic melanoma
title_sort	multiplex immunohistochemistry accurately defines the immune context of metastatic melanoma
publisher	Nature Portfolio
publishDate	2018
url	https://doaj.org/article/1046ef03187a4802bf52b2ca77c01675
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_version_	1718388299801821184

Multiplex immunohistochemistry accurately defines the immune context of metastatic melanoma

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