酰基 CoA 结合蛋白（ACBP，由地西泮结合抑制剂 DBI 编码）通过地西泮和其他苯二氮卓类药物共有的特定结合位点作用于 A 型 γ-氨基丁酸 (GABA) 受体。 ACBP/DBI 和苯二氮卓类药物均充当正变构调节剂，从而增强 GABA 对该受体的作用。最近，我们发现ACBP/DBI作为一种内源性免疫抑制剂，意味着其抗体介导的中和作用具有免疫刺激作用，增强小鼠模型中免疫治疗和化学免疫治疗的疗效。在这些考虑的推动下，我们研究了对小鼠给予地西泮是否会逆转 ACBP/DBI 中和对癌症化学免疫疗法的有益作用。事实上，地西泮废除了抗 ACBP/DBI 抗体的治疗作用，支持了地西泮发挥免疫抑制特性的观点。值得注意的是，与未接受任何精神药物的个体相比，非小细胞肺癌（NSCLC）患者对苯二氮卓类药物的治疗与化学免疫治疗的临床反应较差相关。与苯二氮卓类药物合并使用其他精神药物并不会影响化学免疫治疗的结果，表明这种免疫抑制作用是苯二氮卓类药物特异性的。我们的结论是苯二氮卓类药物可能会产生全身免疫抑制。这一假设需要进一步的流行病学和临床证实。© 2024 作者。经泰勒许可出版

Acyl CoA binding protein (ACBP, which is encoded by diazepam binding inhibitor, DBI) acts on the gamma-amino butyric acid (GABA) receptor type A via a specific binding site that is shared by diazepam and other benzodiazepines. Both ACBP/DBI and benzodiazepines act as positive allosteric modulators, hence increasing GABA effects on this receptor. Recently, we found that ACBP/DBI acts as an endogenous immunosuppressor, meaning that its antibody-mediated neutralization has immunostimulatory effects and enhances the efficacy of immunotherapy and chemoimmunotherapy in mouse models. Driven by these considerations, we investigated whether diazepam administration in mice would reverse the beneficial effects of ACBP/DBI neutralization on cancer chemoimmunotherapy. Indeed, diazepam abolished the therapeutic of anti-ACBP/DBI antibodies, supporting the idea that diazepam exerts immunosuppressive properties. Of note, treatment with benzodiazepines was associated with poor clinical responses to chemoimmunotherapy in patients with non-small cell lung cancer (NSCLC) as compared to individuals not receiving any psychotropic drugs. Medication with other psychotropic drugs than benzodiazepines did not compromise the outcome of chemoimmunotherapy, indicating that this immunosuppressive effect was benzodiazepine specific. We conclude that benzodiazepines may confer systemic immunosuppression. This hypothesis requires further epidemiological and clinical confirmation.© 2024 The Author(s). Published with license by Taylor & Francis Group, LLC.