基于靶向腺苷途径和PD-1/PDL-1轴的联合癌症免疫治疗
Combined cancer immunotherapy based on targeting adenosine pathway and PD-1/PDL-1 axis
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影响因子:4.4
分区:医学2区 / 药学2区
发表日期:2024 Sep
作者:
Mehrdad Fathi, Asieh Zarei, Ata Moghimi, Pooya Jalali, Zahra Salehi, Sharareh Gholamin, Farhad Jadidi-Niaragh
DOI:
10.1080/14728222.2024.2405090
摘要
癌症免疫治疗已彻底改变肿瘤学领域，为晚期恶性肿瘤患者带来了新的希望。肿瘤引起的免疫抑制限制了当前免疫治疗策略的效果，例如PD-1/PDL-1检查点抑制剂。腺苷作为一种嘌呤核苷分子，在这一免疫抑制中起着关键作用，它阻止T细胞激活并促进调节性T细胞的生长。靶向腺苷途径并阻断PD-1/PDL-1，是增强免疫系统对肿瘤反应的潜在途径。本综述讨论了腺苷途径在肿瘤免疫学中的当前理解，以及支持将腺苷途径抑制剂与PD-1/PDL-1阻断结合的临床前和临床数据。我们还讨论了开发针对腺苷途径和PD-1/PDL-1轴的联合免疫治疗以治疗癌症所面临的挑战和未来方向。腺苷信号通路调控许多免疫系统过程，表明其具有广泛的治疗潜力。在未来五年内，该领域将取得巨大进展，恶性肿瘤的治疗护理标准将从单点治疗转变为包含多个信号通路（如腺苷轴）在内的免疫网络整合。
Abstract
Cancer immunotherapy has revolutionized the field of oncology, offering new hope to patients with advanced malignancies. Tumor-induced immunosuppression limits the effectiveness of current immunotherapeutic strategies, such as PD-1/PDL-1 checkpoint inhibitors. Adenosine, a purine nucleoside molecule, is crucial to this immunosuppression because it stops T cells from activating and helps regulatory T cells grow. Targeting the adenosine pathway and blocking PD-1/PDL-1 is a potential way to boost the immune system's response to tumors.This review discusses the current understanding of the adenosine pathway in tumor immunology and the preclinical and clinical data supporting the combination of adenosine pathway inhibitors with PD-1/PDL-1 blockade. We also discuss the challenges and future directions for developing combination immunotherapy targeting the adenosine pathway and the PD-1/PDL-1 axis for cancer treatment.The fact that the adenosine signaling pathway controls many immune system processes suggests that it has a wide range of therapeutic uses. Within the next five years, there will be tremendous progress in this area, and the standard of care for treating malignant tumors will have switched from point-to-point therapy to the integration of immunological networks comprised of multiple signaling pathways, like the adenosine axis.