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|Title:||Multiplex immunohistochemistry accurately defines the immune context of metastatic melanoma.|
|Authors:||Halse, H;Colebatch, A J;Petrone, P;Henderson, M A;Mills, J K;Snow, H;Westwood, J A;Sandhu, S;Raleigh, J M;Behren, Andreas;Cebon, Jonathan S;Darcy, P K;Kershaw, M H;McArthur, G A;Gyorki, D E;Neeson, P J|
|Affiliation:||Cancer Immunology Research, Peter MacCallum Cancer Centre, Melbourne, Australia|
Division of Cancer Medicine Melanoma Program, Peter MacCallum Cancer Centre, Melbourne, Australia
Division of Cancer Surgery, Peter MacCallum Cancer Centre, Melbourne, Australia
Sir Peter MacCallum Department of Oncology, The University of Melbourne, Parkville, Victoria, Australia
Olivia Newton-John Cancer Research Institute, Heidelberg, Victoria, Australia
School of Cancer Medicine, La Trobe University, Bundoora, Australia
Department of Surgery, University of Melbourne, Parkville, Victoria, Australia
|Citation:||Scientific reports 2018; 8(1): 11158|
|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.|
|Appears in Collections:||Journal articles|
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