Conventional type 1 dendritic cells (cDC1) are critical for antitumor immunity, and their abundance within tumors is associated with immune-mediated rejection and the success of immunotherapy.,Here, we show that cDC1 accumulation in mouse tumors often depends on natural killer (NK) cells that produce the cDC1 chemoattractants CCL5 and XCL1.,Similarly, in human cancers, intratumoral CCL5, XCL1, and XCL2 transcripts closely correlate with gene signatures of both NK cells and cDC1 and are associated with increased overall patient survival.,Notably, tumor production of prostaglandin E2 (PGE2) leads to evasion of the NK cell-cDC1 axis in part by impairing NK cell viability and chemokine production, as well as by causing downregulation of chemokine receptor expression in cDC1.,Our findings reveal a cellular and molecular checkpoint for intratumoral cDC1 recruitment that is targeted by tumor-derived PGE2 for immune evasion and that could be exploited for cancer therapy.,•NK cells recruit cDC1 into the tumor microenvironment•cDC1 recruitment depends on NK cell-derived chemokines CCL5 and XCL1•The NK cell/chemokine/cDC1 axis is associated with cancer patient survival•Tumor-derived PGE2 impairs NK cell and cDC1 resulting in cancer immune evasion,NK cells recruit cDC1 into the tumor microenvironment,cDC1 recruitment depends on NK cell-derived chemokines CCL5 and XCL1,The NK cell/chemokine/cDC1 axis is associated with cancer patient survival,Tumor-derived PGE2 impairs NK cell and cDC1 resulting in cancer immune evasion,Natural killer cells recruit dendritic cells to the tumor microenvironment, and disruption of this process results in cancer immune evasion.
Metastatic melanoma, the primary cause of skin cancer-related death, warrants new therapeutic approaches that target the regulatory machinery at molecular level.,While long noncoding RNAs (lncRNAs) are dysregulated in a number of cancer types, limited data are available on the expression and function of lncRNAs in melanoma metastasis.,The primary objective of this study was to investigate the role of 6 metastasis-related lncRNAs in pairs of primary melanoma and matched lymph node metastatic tissues.,Among the tested lncRNAs, HOTAIR was the most highly expressed in lymph node metastasis.,The role of HOTAIR in melanoma cell motility and invasion was further evaluated by knocking down HOTAIR with siRNAs.,Knockdown of HOTAIR resulted in the reduction of motility and invasion of human melanoma cell line A375, as assessed by wound healing assay and Matrigel-based invasion assay. siHOTAIR also suppressed the degradation of gelatin matrix, suggesting that HOTAIR promotes gelatinase activity.,Together, our study shows that HOTAIR is overexpressed in metastatic tissue, which is associated with the ability of HOTAIR to promote melanoma cell motility and invasion.,These data indicate that lncRNAs may be involved in the metastasis of melanoma and provide support for further evaluation of lncRNAs in melanoma.