巨自噬/自噬抑制剂 DBI/ACBP（地西泮结合抑制剂，酰基辅酶 A 结合蛋白）的血浆浓度随着年龄和体重指数 (BMI) 的增加而增加。高龄和肥胖都是癌症发生的最重要的危险因素。我们观察到，由于 BRCA1、BRCA2 和 TP53 突变而患有癌症易感综合征的患者表现出异常高的血浆 DBI/ACBP 水平。此外，与年龄和 BMI 匹配且未患癌症的对照组相比，没有已知癌症易感综合征的患者在即将被诊断为癌症之前（0-3 年内）也表现出较高的 DBI/ACBP 水平。因此，超正常的血浆 DBI/ACBP 构成了后期癌症发展的危险因素。小鼠实验表明，遗传或抗体介导的 DBI/ACBP 抑制可以延缓癌症的发生或进展。在化学免疫治疗的背景下，DBI/ACBP 中和增强了未耗尽的效应 T 细胞对肿瘤的浸润，但减少了调节性 T 细胞的浸润。这使得乳腺癌、非小细胞肺癌和肉瘤模型的癌症得到了更好的控制。我们的结论是，DBI/ACBP 构成了改善癌症免疫监视的可行自噬检查点。缩写：BMI，体重指数； CTL，细胞毒性T淋巴细胞； DBI、地西泮结合抑制剂、酰基辅酶A结合蛋白； mAb，单克隆抗体； NSCLC，非小细胞肺癌； PDCD1/PD-1，程序性细胞死亡1； scRNA-seq，单细胞RNA测序； Treg，调节性T细胞。

The plasma concentration of the macroautophagy/autophagy inhibitor DBI/ACBP (diazepam binding inhibitor, acyl-CoA binding protein) increases with aging and body mass index (BMI). Both advanced age and obesity are among the most important risk factors for the development of cancer. We observed that patients with cancer predisposition syndromes due to mutations in BRCA1, BRCA2 and TP53 exhibit abnormally high plasma DBI/ACBP levels. Additionally, patients without known cancer predisposition syndromes also manifest higher DBI/ACBP levels before imminent cancer diagnosis (within 0-3 years) as compared to age and BMI-matched controls who remain cancer-free. Thus, supranormal plasma DBI/ACBP constitutes a risk factor for later cancer development. Mouse experimentation revealed that genetic or antibody-mediated DBI/ACBP inhibition can delay the development or progression of cancers. In the context of chemoimmunotherapy, DBI/ACBP neutralization enhances tumor infiltration by non-exhausted effector T cells but reduces infiltration by regulatory T cells. This resulted in better cancer control in models of breast cancer, non-small cell lung cancer and sarcoma. We conclude that DBI/ACBP constitutes an actionable autophagy checkpoint for improving cancer immunosurveillance. Abbreviation: BMI, body mass index; CTL, cytotoxic T lymphocyte; DBI, diazepam binding inhibitor, acyl-CoA binding protein; mAb, monoclonal antibody; NSCLC, non-small cell lung cancer; PDCD1/PD-1, programmed cell death 1; scRNA-seq, single-cell RNA sequencing; Treg, regulatory T cell.