二甲双胍介导的增强CD8阳性T细胞肿瘤浸润与增加的肿瘤灌注的相关性

Objective: To investigate the linear correlation between metformin-induced increase in the number of CD8 ⁺ T cells infiltrated into the cancer and metformin-mediated elevation of tumor blood perfusion. Methods: 4T1 murine breast cancer cells were orthotopically injected into the fat pad of the 4th breast of BALB/C mice. Nine days later, the mice were randomly divided into the control and metformin groups. Fifteen minutes before extraction, TRITC-conjugated lectin was injected into the tail vein of the mice. Then, the extracted tumor tissues were prepared for frozen sections, which were then stained with anti-CD8 antibody for further immunofluorescent detection. Spearman correlation analysis was performed to observe the correlation between the parameters. Results: Both the infiltration of CD8 ⁺ T cells [(120.8±26.9)/mm ² vs. (67.9±22.9)/mm ² ] and lectin-perfused area [(18 357.0±5 865.0) pixels/μm ² vs. (10 233.0±4 434.0) pixels/μm ² ] were significantly higher in metformin-treated group than in the untreated group. In both groups, the number of the infiltrated CD8 ⁺ T cells was linearly correlated with lectin-perfused area (control: R=0.884, P=0.007; metformin: R=0.928, P<0.001). Conclusion: Increased tumor perfusion is closely correlated with metformin-induced increase in the infiltration of CD8 ⁺ T cells into the tumor.