浸润的微生物群落代表了固体肿瘤微环境的一种新的细胞成分，可以影响肿瘤的进展和对治疗的反应。肾上腺皮质癌（ACC）是一种罕见而具有侵袭性的内分泌恶性肿瘤，米托酯（MTT）治疗代表了一线治疗，然而其疗效仅局限于治疗窗口水平（14-20 mg/L）。迫切需要新的标志物来预测那些从MTT治疗中受益的患者，以改善患者的管理。我们的研究目的是评估26例人类ACC组织中肿瘤内部细菌微生物组DNA的存在与9例健康肾上腺的相关性；此外，还探讨了相对细菌组成谱、肿瘤质量特征和MTT在治疗早期达到高循环水平的关联性。我们发现细菌DNA存在于所有肿瘤和健康皮质样本的肾上腺中，证实了恶性肿瘤和正常肾上腺之间微生物组成的显著差异：具体来说，ACC组织以较高的变形菌门（尤其是铜绿假单胞菌属和沙门氏菌属）丰度为特点。此外，变形菌门的低丰度与肿瘤大小、Ki67和皮质醇分泌呈负相关。随着治疗9个月后，具高丰度的变形菌门、铜绿假单胞菌属和沙门氏菌属以及低丰度的拟杆菌门、厚壁菌门和链球菌属的ACC患者MTT水平达到较高水平。这些发现首次表明，人类ACC具有浸润细菌，其特定的丰度谱似乎影响了治疗9个月后循环MTT水平的增加。

The infiltrating microbiota represents a novel cellular component of the solid tumour microenvironment that can influence tumour progression and response to therapy. Adrenocortical carcinoma (ACC) is a rare and aggressive endocrine malignancy for which mitotane (MTT) treatment represents the first-line therapy, though its efficacy is limited to a therapeutic window level (14-20 mg/L). Novel markers able to predict those patients who would benefit from MTT therapy are urgently needed to improve patient's management. The aim of our study was to evaluate the presence of intratumoural bacterial microbiota DNA in 26 human ACC tissues vs 9 healthy adrenals; moreover, the association between the relative bacterial composition profile, the tumour mass characteristics and MTT ability to reach high circulating levels in the early phase of treatment, were explored. We found the presence of bacterial DNA in all adrenal samples from both tumours and healthy cortex specimens, documenting significant differences in the microbial composition between malignancy and normal adrenals: in detail, the ACC tissues were characterised by a higher abundance of the Proteobacteria phylum (especially the Pseudomonas and Serratia genera). In addition, the Proteobacteria's low abundance was negatively associated with tumour size, Ki67 and cortisol secretion. MTT levels reached higher levels at 9 months in ACC patients with high abundance of Proteobacteria, Pseudomonas and Serratia and with low abundance of Bacteroidota, Firmicutes and Streptococcus. These findings are the first indication that human ACCs are characterised by infiltrating bacteria and their specific abundance profile seems to influence the increase in circulating MTT levels at 9 months.