MAP4K2 suppresses antitumor immunity in a pancreatic cancer model by promoting Treg differentiation.
1/5 보강
PICO 자동 추출 (휴리스틱, conf 2/4)
유사 논문P · Population 대상 환자/모집단
환자: pancreatic cancer showed increased MAP4K2 levels in infiltrating Treg cells
I · Intervention 중재 / 시술
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C · Comparison 대조 / 비교
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O · Outcome 결과 / 결론
we found that MAP4K2 interacted with DDX39B, induced forkhead box protein P3 (FOXP3) gene expression, and promoted Treg differentiation.
MAP kinase kinase kinase kinase (MAP4K) family kinases are key kinases for T cell-mediated immune responses; however, in vivo roles of MAP4K2 in immune regulation remain unclear.
APA
Chuang HC, Wang CW, et al. (2026). MAP4K2 suppresses antitumor immunity in a pancreatic cancer model by promoting Treg differentiation.. The Journal of clinical investigation, 136(6). https://doi.org/10.1172/JCI196379
MLA
Chuang HC, et al.. "MAP4K2 suppresses antitumor immunity in a pancreatic cancer model by promoting Treg differentiation.." The Journal of clinical investigation, vol. 136, no. 6, 2026.
PMID
41615953 ↗
Abstract 한글 요약
MAP kinase kinase kinase kinase (MAP4K) family kinases are key kinases for T cell-mediated immune responses; however, in vivo roles of MAP4K2 in immune regulation remain unclear. Using T cell-specific Map4k2 conditional knockout (T-Map4k2 cKO) mice, scRNA-seq, and mass spectrometry analysis, we found that MAP4K2 interacted with DDX39B, induced forkhead box protein P3 (FOXP3) gene expression, and promoted Treg differentiation. Mechanistically, MAP4K2 directly phosphorylated the DEAD box protein DDX39B, leading to DDX39B nuclear translocation and subsequent Foxp3 RNA splicing. MAP4K2-induced FOXP3 mRNA levels were abolished in DDX39B knockout T cells. Furthermore, T-Map4k2 cKO mice displayed the reduction of Treg population and the sustained inflammation during remission phase of EAE autoimmune disease model. Remarkably, the anti-PD-1 immunotherapeutic effect on pancreatic cancer was significantly improved in T-Map4k2 cKO mice, Treg-specific Map4k2-deficient mice, adoptively transferred chimeric mice, or MAP4K2-inhibitor-treated mice. Consistently, scRNA-seq analysis of patients with pancreatic cancer showed increased MAP4K2 levels in infiltrating Treg cells. Collectively, MAP4K2 promotes Treg differentiation by inducing DDX39B nuclear translocation, leading to the attenuation of antitumor immunity.
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