Jin Ketao, Mao Chunsen, Chen Lin, Wang Lude, Liu Yuyao, Yuan Jianlie
Department of Colorectal Surgery, Affiliated Jinhua Hospital, Zhejiang University School of Medicine, No. 365, Renmin Eastern Road, Jinhua 321000, Zhejiang, China.
Central Laboratory, Affiliated Jinhua Hospital, Zhejiang University School of Medicine, Jinhua 321000, Zhejiang, China.
Cancers (Basel). 2021 Jan 10;13(2):229. doi: 10.3390/cancers13020229.
Brain tumors comprise different types of malignancies, most of which are originated from glial cells. Glioblastoma multiforme (GBM) is the most aggressive type of brain tumor with a poor response to conventional therapies and dismal survival rates (15 months) despite multimodal therapies. The development of immunotherapeutic strategies seems to be necessary to enhance the overall survival of GBM patients. So far, the immunotherapies applied in GBM had promising results in the primary phases of clinical trials but failed to continue their beneficial effects in later phases. GBM-microenvironment (GME) is a heterogenic and rigorously immunosuppressive milieu wrapping by an impenetrable blood-brain barrier. Hence, in-depth knowledge about the dominant immunosuppressive mechanisms in the GME could foster GBM immunotherapy. Recently, the adenosinergic pathway (AP) is found to be a major player in the suppression of antitumor immune responses in the GME. Tumor cells evolve to metabolize pro-inflammatory ATP to anti-inflammatory adenosine. Adenosine can suppress immune responses through the signaling of adenosine receptors on immune cells. The preclinical results targeting AP in GBM showed promising results in reinvigorating antitumor responses, overriding chemoresistance, and increasing survival. We reviewed the current GBM immunotherapies and elaborated on the role of AP in the immunopathogenesis, treatment, and even prognosis of GBM. We suggest that future clinical studies should consider this pathway in their combination therapies along with other immunotherapeutic approaches.
脑肿瘤包括不同类型的恶性肿瘤，其中大多数起源于神经胶质细胞。多形性胶质母细胞瘤（GBM）是最具侵袭性的脑肿瘤类型，尽管采用了多模式治疗，但对传统治疗反应不佳，生存率极低（15个月）。似乎有必要开发免疫治疗策略来提高GBM患者的总生存率。到目前为止，应用于GBM的免疫疗法在临床试验的初期阶段取得了有希望的结果，但在后期阶段未能继续发挥其有益作用。GBM微环境（GME）是一种异质性且具有严格免疫抑制作用的环境，被难以穿透的血脑屏障包裹着。因此，深入了解GME中主要的免疫抑制机制有助于GBM免疫治疗。最近，发现腺苷能通路（AP）是GME中抑制抗肿瘤免疫反应的主要因素。肿瘤细胞进化为将促炎ATP代谢为抗炎腺苷。腺苷可通过免疫细胞上腺苷受体的信号传导来抑制免疫反应。针对GBM中AP的临床前研究结果显示，在恢复抗肿瘤反应、克服化疗耐药性和提高生存率方面取得了有希望的结果。我们综述了当前的GBM免疫疗法，并阐述了AP在GBM免疫发病机制、治疗甚至预后中的作用。我们建议未来的临床研究在联合治疗中应将该通路与其他免疫治疗方法一起考虑。
