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:Local Ablative Therapy Associated with Immunotherapy in Locally Advanced Pancreatic Cancer: A Solution to Overcome the Double Trouble?-A Comprehensive Review.
Local Ablative Therapy Associated with Immunotherapy in Locally Advanced Pancreatic Cancer: A Solution to Overcome the Double Trouble?-A Comprehensive Review.
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胰腺导管腺癌(PDAC)仍是主要致死性肿瘤,治疗效果不理想,生存率极低,也给临床研究带来挑战。局部晚期不可切除胰腺癌(LAPC)的治疗受到两大问题阻碍:微转移发生率高,以及肿瘤无法手术切除。局部消融治疗除局部作用外,还可诱导全身性抗肿瘤反应,即远隔效应。因此,纳入其他治疗可能是提高免疫治疗临床疗效的关键。本系统综述探讨近期将局部消融治疗与免疫疗法联合用于克服PDAC免疫耐药的研究,并讨论未来前景和挑战。综述特别介绍了4项放化疗研究和9项不可逆电穿孔(IRE)研究。临床上,IRE是首选消融方式,除两项临床试验外,其余试验均采用IRE;它可能形成有利于免疫治疗的微环境。与IRE联用的免疫疗法包括NK细胞或T细胞疗法,以及免疫检查点抑制剂。目前综述所述临床试验结果及这些疗法推进至Ⅱ/Ⅲ期试验的潜力仍不明确。化疗、局部消融和免疫治疗相结合的多模式方案,有望克服LAPC面临的双重困境。
Pancreatic ductal adenocarcinoma (PDAC) remains a major killer and is a challenging clinical research issue with abysmal survival due to unsatisfactory therapeutic efficacy. Two major issues thwart the treatment of locally advanced nonresectable pancreatic cancer (LAPC): high micrometastasis rate and surgical inaccessibility. Local ablative therapies induce a systemic antitumor response (i. e. , abscopal effect) in addition to local effects.
Thus, the incorporation of additional therapies could be key to improving immunotherapy's clinical efficacy. In this systematic review, we explore recent applications of local ablative therapies combined with immunotherapy to overcome immune resistance in PDAC and discuss future perspectives and challenges. Particularly, we describe four chemoradiation studies and nine reports on irreversible electroporation (IRE). Clinically, IRE is the ablative therapy of choice, utilized in all but two clinical trials, and may create a favorable microenvironment for immunotherapy.
Various immunotherapies have been used in combination with IRE, such as NK cell- or T cell-based therapy, as well as immune checkpoint inhibitors. The results of the clinical trials presented in this review and the advancement potential of these therapies to phase II/III trials remain unknown. A multiple treatment approach involving chemotherapy, local ablation, and immunotherapy holds promise in overcoming the double trouble of LAPC.
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