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.
Mucosal melanomas in the head and neck region are most frequently located in the nasal cavity and paranasal sinuses.,Sinonasal mucosal melanoma (SNMM) comprises <1% of all melanomas.,The aim was to determine the KIT, NRAS and BRAF mutation frequencies in a large series of primary SNMMs.,Laser capture microdissection was used to isolate tumour cells from 56 formalin-fixed paraffin-embedded tumours.,The tumour cells were screened for KIT, NRAS and BRAF mutations by direct sequencing.,Overall, 21% (12 out of 56) of SNMMs harboured KIT, NRAS or BRAF mutations.,Mutations in these oncogenes occurred in a mutually exclusive manner.,Both KIT and BRAF mutations were identified at a similar frequency of 4% each (2 out of 56), whereas NRAS mutations were detected in 14% (8 out of 56) of the SNMMs.,Four of the NRAS mutations were located in exon 1.,Mutations in these oncogenes were significantly more common in melanomas located in the paranasal sinuses than in nasal cavity (P=0.045).,In a multivariate analysis, patients with melanomas in the nasal cavity had a significantly better overall survival than those with tumours in the paranasal sinuses (P=0.027).,Our findings show that KIT and BRAF mutations, which are accessible for present targeted therapies, are only rarely present in SNMMs, whereas NRAS mutations seem to be relatively more frequent.,The data show that majority of SNMMs harbour alterations in genes other than KIT, NRAS and BRAF.