Functional heterogeneity of lymphocytic patterns in primary melanoma dissected through single-cell multiplexing

In melanoma, the lymphocytic infiltrate is a prognostic parameter classified morphologically into 'brisk', 'non-brisk' and 'absent' entailing a functional association that has never been proved. Recently, it has been shown that lymphocytic populations can be very hetero...

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Bibliographic Details
Published in:eLife 2020-02, Vol.9
Main Authors: Bosisio, Francesca Maria, Antoranz, Asier, van Herck, Yannick, Bolognesi, Maddalena Maria, Marcelis, Lukas, Chinello, Clizia, Wouters, Jasper, Magni, Fulvio, Alexopoulos, Leonidas, Stas, Marguerite, Boecxstaens, Veerle, Bechter, Oliver, Cattoretti, Giorgio, van den Oord, Joost
Format: Article
Language:English
Subjects:
Analysis
brisk
Cancer Biology
Classification
Datasets
Gene expression
Humans
Image processing
Image processing equipment
Immunotherapy
Inflammation
Lymphocytes
Lymphocytes T
Lymphocytes, Tumor-Infiltrating - immunology
Medical prognosis
Melanoma
Melanoma - immunology
Melanoma - pathology
microenvironment
Morphology
multiplex
Patients
PD-1 protein
Polymerase chain reaction
Proteomics
Single-Cell Analysis - methods
Skin Neoplasms - immunology
Skin Neoplasms - pathology
Survival analysis
T cells
TILs
Tumor Microenvironment
tumor-infiltrating lymphocytes
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Summary:In melanoma, the lymphocytic infiltrate is a prognostic parameter classified morphologically into 'brisk', 'non-brisk' and 'absent' entailing a functional association that has never been proved. Recently, it has been shown that lymphocytic populations can be very heterogeneous, and that anti-PD-1 immunotherapy supports activated T cells. Here, we characterize the immune landscape in primary melanoma by high-dimensional single-cell multiplex analysis in tissue sections (MILAN technique) followed by image analysis, RT-PCR and shotgun proteomics. We observed that the brisk and non-brisk patterns are heterogeneous functional categories that can be further sub-classified into active, transitional or exhausted. The classification of primary melanomas based on the functional paradigm also shows correlation with spontaneous regression, and an improved prognostic value when compared to that of the brisk classification. Finally, the main inflammatory cell subpopulations that are present in the microenvironment associated with activation and exhaustion and their spatial relationships are described using neighbourhood analysis.
ISSN:2050-084X
2050-084X
DOI:10.7554/eLife.53008