@article{oai:nagoya.repo.nii.ac.jp:00031068,
 author = {Kumagai, Shogo and Togashi, Yosuke and Sakai, Chika and Kawazoe, Akihito and Kawazu, Masahito and Ueno, Toshihide and Sato, Eiichi and Kuwata, Takeshi and Kinoshita, Takahiro and Yamamoto, Masami and Nomura, Sachiyo and Tsukamoto, Tetsuya and Mano, Hiroyuki and Shitara, Kohei and Nishikawa, Hiroyoshi},
 issue = {1},
 journal = {Immunity},
 month = {Jul},
 note = {Only a small percentage of patients afflicted with gastric cancer (GC) respond to immune checkpoint blockade (ICB). To study the mechanisms underlying this resistance, we examined the immune landscape of GC. A subset of these tumors was characterized by high frequencies of regulatory T (Treg) cells and low numbers of effector T cells. Genomic analyses revealed that these tumors bore mutations in RHOA that are known to drive tumor progression. RHOA mutations in cancer cells activated the PI3K-AKT-mTOR signaling pathway, increasing production of free fatty acids that are more effectively consumed by Treg cells than effector T cells. RHOA mutant tumors were resistant to PD-1 blockade but responded to combination of PD-1 blockade with inhibitors of the PI3K pathway or therapies targeting Treg cells. We propose that the metabolic advantage conferred by RHOA mutations enables Treg cell accumulation within GC tumors, generating an immunosuppressive TME that underlies resistance to ICB., ファイル公開：2021-07-14},
 pages = {187--203.e8},
 title = {An Oncogenic Alteration Creates a Microenvironment that Promotes Tumor Progression by Conferring a Metabolic Advantage to Regulatory T Cells},
 volume = {53},
 year = {2020}
}