Programa de Pós-Graduação Em Ciências Biológicas: Bioquímica, Instituto de Ciências Básicas da Saúde, UFRGS, Porto Alegre, RS, Brazil.
Programa de Pós-Graduação Em Pediatria E Saúde da Criança, Escola de Medicina, PUCRS, Porto Alegre, RS, Brazil.
Purinergic Signal. 2024 Feb;20(1):47-64. doi: 10.1007/s11302-023-09931-4. Epub 2023 Mar 24.
Malignant gliomas are highly heterogeneous glia-derived tumors that present an aggressive and invasive nature, with a dismal prognosis. The multi-dimensional interactions between glioma cells and other tumor microenvironment (TME) non-tumoral components constitute a challenge to finding successful treatment strategies. Several molecules, such as extracellular purines, participate in signaling events and support the immunosuppressive TME of glioma patients. The purinergic signaling and the ectoenzymes network involved in the metabolism of these extracellular nucleotides are still unexplored in the glioma TME, especially in lower-grade gliomas (LGG). Also, differences between IDH-mutant (IDH-Mut) versus wild-type (IDH-WT) gliomas are still unknown in this context. For the first time, to our knowledge, this study characterizes the TME of LGG, high-grade gliomas (HGG) IDH-Mut, and HGG IDH-WT patients regarding purinergic ectoenzymes and P1 receptors, focusing on tumor-infiltrating lymphocytes. Here, we show that ectoenzymes from both canonical and non-canonical pathways are increased in the TME when compared to the peripheral blood. We hypothesize this enhancement supports extracellular adenosine generation, hence increasing TME immunosuppression.
恶性神经胶质瘤是高度异质性的神经胶质来源的肿瘤，具有侵袭性和侵略性，预后不良。神经胶质瘤细胞与其他肿瘤微环境（TME）非肿瘤成分之间的多维相互作用，给寻找成功的治疗策略带来了挑战。几种分子，如细胞外嘌呤，参与信号事件，并支持神经胶质瘤患者的免疫抑制性 TME。嘌呤能信号和参与这些细胞外核苷酸代谢的外切酶网络在神经胶质瘤 TME 中仍未被探索，特别是在低级别神经胶质瘤（LGG）中。此外，在这种情况下，IDH 突变型（IDH-Mut）与野生型（IDH-WT）神经胶质瘤之间的差异仍然未知。据我们所知，这项研究首次对 LGG、高级别神经胶质瘤（HGG）IDH-Mut 和 HGG IDH-WT 患者的 TME 中的嘌呤外切酶和 P1 受体进行了特征描述，重点是肿瘤浸润淋巴细胞。在这里，我们表明，与外周血相比，TME 中的经典和非经典途径的外切酶都增加了。我们假设这种增强支持细胞外腺苷的产生，从而增加 TME 的免疫抑制作用。
