Diverse fibroblastic populations in human melanoma microenvironment and their relationship with T cells
Jennifer Eom1,2, Saem Mul Park1,2, Jennifer Chen1, Anna Brooks1,2, Julie McIntosh1, Claudia Mansell1, Vaughan Feisst1, 2, Rod Dunbar1,2
1School of Biological Sciences, The University of Auckland, Auckland, New Zealand, 2Maurice Wilkins Centre for Molecular Biodiscovery, Auckland, New Zealand
Tumor-Associated Fibroblasts (TAFs) are one of the key players controlling immune cell activity in tumors. However, ambiguity around their molecular phenotype and cellular origin hinders exploration of their full potential as therapeutic targets in cancer immunotherapy. Therefore we sought to characterize mesenchymal populations in the microenvironment of human melanoma using 16-color flow cytometry coupled with 4-color immunofluorescence microscopy that had previously allowed us to identify novel mesenchymal precursor populations in dermis1 and lymph nodes from healthy donors. We have identified several distinct populations of mesenchymal cells in melanoma-infiltrated tissue, including a population that corresponds with mesenchymal precursor cells in metastases to both dermis and lymph node. Upregulation of several markers (including FAP and CD26) indicates both fibroblastic and mesenchymal precursor populations are activated following melanoma infiltration. These populations show distinctive spatial relationships with T lymphocytes, although these vary between individual patients. We are currently investigating how these distinct mesenchymal populations each modulate T cell function.
1Feisst, V., Brooks, A. E. S., Chen, C.-J. J. & Dunbar, P. R. Characterization of mesenchymal progenitor cell populations directly derived from human dermis. Stem Cells Dev. 23, 631–42 (2014).