RNF43 p.G659fs 通过 PI3K/AKT/mTOR 信号通路和 HLA-E 上调导致 MSI-high 结直肠癌中 NK 细胞功能障碍
RNF43 p.G659fs leads to natural killer cell dysfunction in MSI-high colorectal cancer through PI3K/AKT/mTOR signaling and HLA-E up-regulation.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Advancing Adjuvant Immunotherapy in Hepatocellular Carcinoma: A Comprehensive Review.
Advancing Adjuvant Immunotherapy in Hepatocellular Carcinoma: A Comprehensive Review.
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肝细胞癌(HCC)仍然是全球癌症相关死亡的主要原因,即使在接受肝切除术和肝移植(LT)等根治性治疗后,复发率仍然很高。近年来,免疫检查点抑制剂(ICIs)改变了HCC的治疗格局,通过联合方案如抗程序性细胞死亡配体-1(PD-L1)/PD-1抑制剂联合抗血管内皮生长因子药物,在晚期肿瘤中显示出显著疗效。近期进展突出了ICIs作为辅助治疗改善高危患者切除术后无复发生存的潜力。
然而,低免疫原性、免疫抑制性肿瘤微环境和免疫耐药等挑战仍然是ICIs取得更广泛成功的重大障碍。在LT的背景下,ICIs的使用因同时需要使用免疫抑制剂而进一步复杂化,这可能加剧复发风险。新兴策略聚焦于优化ICI治疗时机和利用新型生物标志物,正在探索以在维持抗肿瘤疗效的同时减轻移植物排斥。
此外,基于嵌合抗原受体-T和自然杀伤(NK)细胞的免疫细胞疗法、过继细胞转移以及肝脏驻留NK细胞方法也正在研究其减少复发和改善生存结局的潜力。本综述聚焦于辅助免疫治疗和免疫细胞治疗在HCC术后管理中的当前格局,重点介绍正在进行的临床试验、治疗潜力及相关风险。随着免疫治疗策略和个性化方法的持续进步,这些疗法有望改变接受根治性切除或LT患者的结局。
Hepatocellular carcinoma (HCC) remains a leading cause of cancer-related mortality globally, with high rates of recurrence even after curative-intent treatments such as hepatectomy and liver transplantation (LT).
In recent years, immune checkpoint inhibitors (ICIs) have transformed the therapeutic landscape for HCC, demonstrating significant efficacy among advanced-stage tumors through combination regimens, such as anti-programmed cell death ligand-1 (PD-L1)/PD-1 inhibitors with anti-vascular endothelial growth factor agents. Recent advances have highlighted the potential of ICIs as adjuvant therapy to improve recurrence-free survival among high-risk patients post-resection.
However, challenges such as low immunogenicity, the immunosuppressive tumor microenvironment, and immune resistance remain substantial barriers to the broader success of ICIs. In the context of LT, the use of ICIs is further complicated by the concurrent need for immunosuppressive agents, which can exacerbate the risk of recurrence. Emerging strategies focusing on the optimization of the timing of ICI therapy and the utilization of novel biomarkers are being explored to mitigate graft rejection while maintaining antitumor efficacy.
Additionally, immune-cell-based therapies based on chimeric antigen receptor-T and natural killer (NK) cells, adoptive cell transfer, and liver-resident NK cell approaches are also being investigated for their potential to reduce recurrence and improve survival outcomes.
This review focuses on the current landscape of adjuvant immunotherapy and immune-cell therapy in the postoperative management of HCC, highlighting ongoing clinical trials, therapeutic potential, and associated risks. With continued advancements in immunotherapeutic strategies and personalized approaches, these therapies hold the promise of transforming outcomes for patients undergoing curative resection or LT.
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