Single-cell dissection of mature conventional dendritic cells in the tumor microenvironment in metastatic melanoma

Abstract

Although immunotherapy has revolutionized cancer treatment, the response rate of metastatic melanoma to immune checkpoint inhibitors (ICI) remains at less than 50%. One of the determinants of response might be explained by the underlying molecular mechanisms in the tumor microenvironment (TME), which is the composition of tumor cells and its surrounding environment of other cell types which play various roles in facilitating or inhibiting the progression of cancer. It was in our interest to specifically investigate the immunological factors driving observed clinical outcomes. Using single-cell technologies, mature conventional dendritic cells (mDCs) were identified in a cohort of metastatic melanoma samples and were present at a higher proportion in a subset of ICI anti-PD1-treated patients with better progression free survival (PFS). Elaborating on this finding, we generalized the characterization of mDCs in metastatic melanoma by using methods to determine mDCs’ association with other subtypes found in the TME, reveal the molecular features of mDCs compared to other conventional dendritic cells (cDCs), and find differentiating factors among samples with different mDC proportions. Through computational analysis of single-cell transcriptomes and epigenomes in metastatic melanoma, we aim to uncover critical immunological features and interactions within the TME, with potential for enhancing melanoma outcomes.