Core Viewpoint - The study reveals a new mechanism by which lactate in the tumor microenvironment inhibits the anti-tumor function of natural killer (NK) cells through lactylation modification, providing new intervention targets and strategies to enhance NK cell cytotoxicity [1][3]. Group 1 - The research indicates that elevated levels of lysine lactylation (Kla) in NK cells are associated with impaired NAD metabolism, mitochondrial fragmentation, and reduced cytotoxicity [3]. - Supplementation with nicotinamide riboside (NR) and honokiol, a SIRT3 activator, enhances NK cell cytotoxicity by lowering intracellular Kla levels [3]. - The combination of NR and honokiol regulates Kla's effect on the protein kinase ROCK1, inhibiting the ROCK1-DRP1 signaling pathway to prevent mitochondrial fragmentation and restore NK cell activity against leukemia both in vivo and in vitro [3]. Group 2 - The study emphasizes that lactate-induced lactylation represents a new target for immunotherapy based on NK cells, aiming to enhance their tolerance to lactate within the tumor microenvironment [5]. - The research was conducted by a collaborative team from the University of Science and Technology of China and Fudan University, with key contributors including researchers Jin Jing, Yan Peidong, and Wang Dongyao [5].