Anti-neoplastic sulfonamides alter the metabolic homeostasis and disrupt the suppressor activity of regulatory T cells.

Regulatory T cells (Tregs) are essential to maintain self-tolerance and immune homeostasis but, as components of the tumor microenvironment (TME), are also a major barrier to effective cancer immunosurveillance and immunotherapy. FH535 and its derivative Y3 are two N-aryl-benzene-sulfonamides (NABs) that inhibit HCC cell proliferation and tumor progression. However, the impact of NABs on the immune cells in the TME is not yet known. Analyses of explanted livers from patients with hepatocellular carcinoma (HCC) showed that high levels of tumor-infiltrating Tregs were associated with poor tumor differentiation. These results lead us to investigate the immunomodulatory effects of NABs in regulatory and effector T cells. Exposure of primary human Tregs to NABs induced a rapid but temporary increase of cell expansion, a gradual disruption of suppressor activity, and concomitant bioenergetics and autophagic flux dysregulations. In contrast to Tregs, no gross effects were observed in effector T cells. Addition of Rapamycin prevented the functional decay of Tregs and restored their metabolic profile, suggesting that NAB effects require the integrity of the mTOR pathway. This study revealed the immunomodulatory properties of NABs with a preferential impact on Treg activity and provided novel insights into the anti-tumor potential of sulfonamides.

Bilateral aberrant infratentorial vasculature: a rare cadaveric encounter

During a cadaveric dissection course, abnormalities of the infratentorial vasculature were noted. Following removal of the brain, the posterior cranial fossa showed the left labyrinthine artery splitting into two branches: one entered the internal auditory meatus (IAM) with the eighth cranial nerve, and the other pierced the petrous temporal bone just posterior to the IAM in the region of the subarcuate fossa. On the right side, the anterior inferior cerebellar artery formed a loop that was embedded in the dura just posterior to the IAM, but no vessels were seen entering the IAM. Further dissection into the petrous temporal bone showed the loop directed towards the region of the subarcuate fossa, and the injection of coloured latex confirmed fine arterial distribution of the latex on the surface of the deep part of the eighth cranial nerve. Eight other cadavers dissected in the same course did not show any such anomalies. Knowledge of these vascular variations is important for surgical exposure of the posterior cranial fossa

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