Inflammatory transcript signatures and activated regulatory T lymphocytes in melanoma metastases
Purpose: to study the correlations between transcriptional signatures reflecting the abundance and functional activity of tumor-infiltrating inflammatory cells from RNA-seq data on one hand, and the number of intratumoral activated regulatory T lymphocytes Methods: Gene expression profiles of 19 snap-frozen cutaneous metastases from 19 melanoma patients were obtained by RNA-seq of poly-A RNA. Cryosections from the same tumors were stained by multiplexed immunofluorescence for GARP and FoxP3. FoxP3+GARP+ activated regulatory T lymphocytes (Treg) were quantified by computerized image analysis. Correlations between the proportion of activated Treg and gene expression signatures of inflammatory cells and pathways were analyzed by Gene Set Enrichment Analysis. Results:  The genes whose expression level correlated the most with the proportion of activated Tregs were significantly enriched for genes expressed by T lymphocytes and for genes induced by IFN-gamma, TNF-alpha, IL-1-beta and TGF-beta, including genes induced by TGF-beta in effector T cells. Conclusions: Our  results in this small series of melanoma samples suggest that Treg infiltration and Treg-dependent TGF-beta activity are proportional to T-cell infiltration and effector activity in tumors. Overall design: mRNA profiles of cutaneous melanoma metastases