2026-04-29T04:09:30Zhttps://repisalud.isciii.es/rest/oai/request

oai:repisalud.isciii.es:20.500.12105/231122024-11-29T23:57:32Zcom_20.500.12105_2173com_20.500.12105_2051col_20.500.12105_19597

00925njm 22002777a 4500 dc Park, Matthew D author Reyes-Torres, Ivan author LeBerichel, Jessica author Hamon, Pauline author LaMarche, Nelson M author Hegde, Samarth author Belabed, Meriem author Troncoso, Leanna author Grout, John A author Magen, Assaf author Humblin, Etienne author Nair, Achuth author Molgora, Martina author Hou, Jinchao author Newman, Jenna H author Farkas, Adam M author Leader, Andrew M author Dawson, Travis author D'Souza, Darwin author Hamel, Steven author Sanchez-Paulete, Alfonso Rodriguez author Maier, Barbara author Bhardwaj, Nina author Martin, Jerome C author Kamphorst, Alice O author Kenigsberg, Ephraim author Casanova-Acebes, Maria author Horowitz, Amir author Brown, Brian D author De Andrade, Lucas Ferrari author Colonna, Marco author Marron, Thomas U author Merad, Miriam author 2023-05 Natural killer (NK) cells are commonly reduced in human tumors, enabling many to evade surveillance. Here, we sought to identify cues that alter NK cell activity in tumors. We found that, in human lung cancer, the presence of NK cells inversely correlated with that of monocyte-derived macrophages (mo-macs). In a murine model of lung adenocarcinoma, we show that engulfment of tumor debris by mo-macs triggers a pro-tumorigenic program governed by triggering receptor expressed on myeloid cells 2 (TREM2). Genetic deletion of Trem2 rescued NK cell accumulation and enabled an NK cell-mediated regression of lung tumors. TREM2+ mo-macs reduced NK cell activity by modulating interleukin (IL)-18/IL-18BP decoy interactions and IL-15 production. Notably, TREM2 blockade synergized with an NK cell-activating agent to further inhibit tumor growth. Altogether, our findings identify a new axis, in which TREM2+ mo-macs suppress NK cell accumulation and cytolytic activity. Dual targeting of macrophages and NK cells represents a new strategy to boost antitumor immunity. Nat Immunol . 2023;24(5):792-801 https://hdl.handle.net/20.500.12105/23112 37081148 10.1038/s41590-023-01475-4 1529-2916 Nature immunology TREM2 macrophages drive NK cell paucity and dysfunction in lung cancer