ALKhemeiri Nasrah, Eljack Sahar, Saber-Ayad Maha Mohamed
College of Graduate Studies, University of Sharjah, Sharjah P.O. Box 27272, United Arab Emirates.
Sharjah Institute for Medical Research, University of Sharjah, Sharjah P.O. Box 27272, United Arab Emirates.
Cells. 2025 May 20;14(10):745. doi: 10.3390/cells14100745.
Colorectal cancer (CRC) is the third most common cancer in the world, with increasing incidence and mortality rates. Standard conventional treatments for CRC are surgery, chemotherapy, and radiotherapy. Recently, immunotherapy has been introduced as a promising alternative to CRC treatment that utilizes patients' immune system to combat cancer cells. The beneficial effect of immune checkpoint inhibitors, specifically anti-PD-1/ PD-L1, has been ascribed to the abundance of DNA replication errors that result in the formation of neoantigens. Such neoantigens serve as distinct flags that amplify the immune response when checkpoint inhibitors (ICIs) are administered. DNA replication errors in CRC patients are expressed as two statuses: the first is the deficient mismatch repair (MSI-H/dMMR) with a higher overall immune response and survival rate than the second status of patients with proficient mismatch repair (MSS/pMMR). There is a limitation to using anti-PD-1/PD-L1 as it is only confined to MSI-H/dMMR, where there is an abundance of T-cell inhibitory ligands (PD-L1). This calls for investigating new therapeutic interventions to widen the scope of ICIs' role in the treatment of CRC. Autophagy modulation provides a good example. Autophagy is a cellular process that plays a crucial role in maintaining cellular homeostasis and has been studied for its impact on tumor development, progression, and response to treatment. In this review, we aim to highlight autophagy as a potential determinant in tumor immune response and to study the impact of autophagy on the tumor immune microenvironment. Moreover, we aim to investigate the value of a combination of anti-PD-1/PD-L1 agents with autophagy modulators as an adjuvant therapeutic approach for CRC treatment.
结直肠癌（CRC）是全球第三大常见癌症，其发病率和死亡率呈上升趋势。CRC的标准传统治疗方法是手术、化疗和放疗。最近，免疫疗法作为一种有前景的CRC治疗替代方法被引入，它利用患者的免疫系统对抗癌细胞。免疫检查点抑制剂，特别是抗PD - 1/PD - L1的有益效果归因于大量的DNA复制错误，这些错误导致新抗原的形成。当给予检查点抑制剂（ICIs）时，此类新抗原作为独特的标志放大免疫反应。CRC患者的DNA复制错误表现为两种状态：第一种是错配修复缺陷（MSI - H/dMMR），其总体免疫反应和生存率高于第二种错配修复 proficient（MSS/pMMR）状态的患者。使用抗PD - 1/PD - L1存在局限性，因为它仅适用于MSI - H/dMMR，这类患者中存在大量T细胞抑制性配体（PD - L1）。这就需要研究新的治疗干预措施，以扩大ICIs在CRC治疗中的作用范围。自噬调节就是一个很好的例子。自噬是一个在维持细胞稳态中起关键作用的细胞过程，其对肿瘤发生、发展和治疗反应的影响已得到研究。在本综述中，我们旨在强调自噬作为肿瘤免疫反应的潜在决定因素，并研究自噬对肿瘤免疫微环境的影响。此外，我们旨在研究抗PD - 1/PD - L1药物与自噬调节剂联合作为CRC辅助治疗方法的价值。
