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.
All data generated or analysed during this study are included in the submission as source data files. We also included the codes to ease the review in process.
TCGA-SKCMTCGA, TCGSKCM phs000178.
- Francesca Maria Bosisio
- Asier Antoranz
- Maddalena Maria Bolognesi
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Human subjects: Ethical approval was obtained from the Ethical Committee/IRB OG032 of the University Hospital of Leuven. After the approval, the study was identified with the number S57266. According to the Clinical Trial regalement no informed consent was needed due to the use of post-diagnostic left-over material.
- C Daniela Robles-Espinoza, International Laboratory for Human Genome Research, Mexico
© 2020, Bosisio et al.
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