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:Low-Toxicity Natural Killer Cell-Based Immunotherapy for NRAS-Driven Mucosal Melanoma: Advances in Immune Regenerative Medicine.
Low-Toxicity Natural Killer Cell-Based Immunotherapy for NRAS-Driven Mucosal Melanoma: Advances in Immune Regenerative Medicine.
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肛管直肠黏膜黑色素瘤(AMM)是一种罕见且侵袭性强的癌症,治疗选择有限,构成重大挑战。目前AMM的标准治疗存在明显缺陷,常导致疾病复发和进展,最终使晚期AMM患者预后不良。显然,迫切需要创新治疗策略以改善AMM病例的结局。在本报告中,详细描述了一种用于治疗晚期黏膜黑色素瘤的开创性个性化n-of-one方法。这一开创性方法涉及利用低剂量免疫治疗作为免疫再生医学(IRM)方案。该治疗方案基于对血浆来源的无细胞循环肿瘤DNA(ctDNA)进行液体活检分析及突变谱检测来量身定制。该方法旨在增强患者对疾病的免疫反应、降低肿瘤负荷并尽量减少不良反应。这一引人注目的病例研究展示了一名66岁男性复发性III期AMM患者。尽管接受了包括多次手术、放疗和免疫检查点抑制剂(ICI)治疗在内的标准治疗,疾病仍持续进展。
然而,在低剂量白细胞介素-2(IL-2)免疫治疗后,患者的免疫功能出现显著改善,尤其是自然杀伤(NK)细胞数量和活性。此外,癌症出现消退,突出表现为NRAS Q61R驱动突变显著减少以及BRCA2 A3012P突变消失。这些令人鼓舞的结果表明,聚焦NK细胞的个性化精准免疫治疗可能有望彻底改变已用尽常规治疗的AMM患者的治疗格局。
值得注意的是,该患者副作用极小,并避免了毒性相关并发症。虽然需要进一步研究以验证这些发现,但这种方法作为这种侵袭性癌症类型的可行管理策略的前景是令人鼓舞的。
Anorectal mucosal melanoma (AMM) poses a significant challenge as a rare and aggressive cancer with limited treatment options. The current standard treatments for AMM have notable drawbacks, often leading to disease recurrence and progression, ultimately resulting in a poor prognosis for patients with advanced AMM. The critical necessity for innovative therapeutic strategies to enhance outcomes in AMM cases is evident. In this report, a groundbreaking personalized (n) of one approach was detailed for the treatment of advanced mucosal melanoma.
This pioneering method involves utilizing low-dose immunotherapy as an immune regenerative medicine (IRM) regimen. The treatment plan is tailored based on liquid biopsy analysis of plasma-derived cell-free circulating tumor DNA (ctDNA) with mutational profiling.
This approach aims to enhance the patient's immune response to the disease, reduce tumor burden, and minimize adverse effects. This compelling case study showcased a 66-year-old male with recurrent stage III AMM. Despite undergoing standard therapies with multiple surgeries, radiation therapy, and immune checkpoint inhibitor (ICI) treatment, disease progression persisted.
However, post low-dose interleukin-2 (IL-2) immunotherapy, notable improvements were observed in the patient's immune function, particularly in natural killer (NK) cell number and activity.
Additionally, the cancer exhibited regression, highlighted by a significant decrease in NRAS Q61R driver mutations and the absence of the BRCA2 A3012P mutation. These encouraging results suggest that personalized precision immunotherapy focusing on NK cells could potentially revolutionize the treatment landscape for AMM patients who have exhausted conventional therapies.
Notably, the patient experienced minimal side effects and avoided toxicity-related complications. While further research is essential to validate these findings, the prospect of this approach as a viable management strategy for this aggressive cancer type is promising.
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