Ontology type: schema:ScholarlyArticle Open Access: True
2018-12
AUTHORSH. 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
ABSTRACTA 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. More... »
PAGES11158
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DOIhttp://dx.doi.org/10.1038/s41598-018-28944-3
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63 URIs
21 LITERALS
9 BLANK NODES