Department of General Surgery, The First Hospital of Lanzhou University, Lanzhou, China.
Department of Stomatology, The First Hospital of Lanzhou University, Lanzhou, China.
Cancer Med. 2023 Nov;12(21):20573-20589. doi: 10.1002/cam4.6623. Epub 2023 Oct 20.
Gastrointestinal cancer poses a serious health threat owing to its high morbidity and mortality. Although immune checkpoint blockade (ICB) therapies have achieved meaningful success in most solid tumors, the improvement in survival in gastrointestinal cancers is modest, owing to sparse immune response and widespread resistance. Metabolic reprogramming, autophagy, and ferroptosis are key regulators of tumor progression.
A literature review was conducted to investigate the role of the metabolic reprogramming, autophagy, and ferroptosis in immunotherapy resistance of gastrointestinal cancer.
Metabolic reprogramming, autophagy, and ferroptosis play pivotal roles in regulating the survival, differentiation, and function of immune cells within the tumor microenvironment. These processes redefine the nutrient allocation blueprint between cancer cells and immune cells, facilitating tumor immune evasion, which critically impacts the therapeutic efficacy of immunotherapy for gastrointestinal cancers. Additionally, there exists profound crosstalk among metabolic reprogramming, autophagy, and ferroptosis. These interactions are paramount in anti-tumor immunity, further promoting the formation of an immunosuppressive microenvironment and resistance to immunotherapy.
Consequently, it is imperative to conduct comprehensive research on the roles of metabolic reprogramming, autophagy, and ferroptosis in the resistance of gastrointestinal tumor immunotherapy. This understanding will illuminate the clinical potential of targeting these pathways and their regulatory mechanisms to overcome immunotherapy resistance in gastrointestinal cancers.
胃肠道癌发病率和死亡率高，对健康构成严重威胁。尽管免疫检查点阻断（ICB）疗法在大多数实体瘤中取得了显著的成功，但胃肠道癌的生存改善仍较为有限，这归因于免疫反应稀疏和广泛的耐药性。代谢重编程、自噬和铁死亡是肿瘤进展的关键调节因素。
我们进行了文献回顾，以研究代谢重编程、自噬和铁死亡在胃肠道癌免疫治疗耐药中的作用。
代谢重编程、自噬和铁死亡在调节肿瘤微环境中免疫细胞的存活、分化和功能方面发挥着关键作用。这些过程重新定义了癌细胞和免疫细胞之间的营养分配蓝图，促进肿瘤免疫逃逸，这对胃肠道癌免疫治疗的疗效有重大影响。此外，代谢重编程、自噬和铁死亡之间存在深刻的相互作用。这些相互作用在抗肿瘤免疫中至关重要，进一步促进了免疫抑制微环境的形成和对免疫治疗的耐药性。
因此，有必要对代谢重编程、自噬和铁死亡在胃肠道肿瘤免疫治疗耐药中的作用进行全面研究。这一认识将阐明靶向这些途径及其调节机制以克服胃肠道癌免疫治疗耐药性的临床潜力。
