Investigation of the ROle of faT and inflAmmaTory Cells in mElanoma

A Clinical, Histological, Cellular and Molecular Investigation of the Role of Fat and Inflammatory Cells in Melanoma Plasticity and Metastases

This study is a retrospective, proof-of-concept sample study to investigate a novel histological finding within the primary melanoma tumour in a large population of melanoma patients to assess its prognostic significance.

This is a aims to validate the striking observation that a cross-talk between fat cells and leukocytes at the primary melanoma site promotes metastasis. In our unpublished pilot study, we have discovered an interesting finding whereby inflammatory cells extend from the tumour to and invading fat in the subcutaneous tissue and/or around the appendageal structures in the dermal skin in metastatic melanomas with distinct architectural changes within the fat. This finding was consistently present in metastatic and absent in non-metastatic melanomas. This new finding has both clinical and pathophysiological credence. Archival tissue blocks or human cell lines will be used in the first instance. As mitigation, experiments will be repeated with conditioned media obtained from co-culture of mixed primary immune cells obtained from peripheral blood mononuclear cell (PBMCs) and adipocytes induced from stem cells.

This study aims to:

• Investigate if the crosstalk between fat cells and tumour-infiltrating inflammatory cells defines the aggressiveness of primary cutaneous melanomas.
• Identify and perform biological spatial analysis of the inflammatory cells between the tumour and fat in the primary tumours.
• Investigate the interactions of fat cells and/or inflammatory cells in mediating melanoma cellular plasticity.

The patients have not provided consent and will be justified in this application

Inclusion Criteria:

1. Melanomas treated between 1st January 2006 and 31st December 2015 OR

2. Patients treated at the Christie between 2014 and 2019.

3. Review of histological slides for presence or absence of relevant histological features.

   For group 3 and group 4:

4. Unique features of spitzoid melanomas

Exclusion Criteria:

• Inadequate slide quality
• Unable to view the entire cross section of the skin with the primary tumour hence, unable to assess the invasion of inflammatory cells into fat