NK cells stimulate recruitment of cDC1 into the tumor microenvironment promoting cancer immune control
journal contributionposted on 2020-07-01, 11:11 authored by Jan P Böttcher, Eduardo Bonavita, Probir Chakravarty, Hanna Blees, Mar Cabeza Cabrerizo, Stefano Sammicheli, Neil C Rogers, Erik Sahai, Santiago Zelenay, Caetano Reis e Sousa
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.
cancer immunotherapydendritic cellsimmune evasiontumor immune controltumor microenvironmentAnimalsCell Line, TumorChemokine CCL5Chemokines, CCyclooxygenase 1Cyclooxygenase 2Dendritic CellsDinoprostoneGene Expression Regulation, NeoplasticHumansKiller Cells, NaturalMelanomaMiceMutationNeoplasmsPrognosisProto-Oncogene Proteins B-rafSurvival AnalysisTumor MicroenvironmentReis e Sousa FC001136Sahai FC001144CBDevelopmental Biology06 Biological Sciences11 Medical and Health Sciences