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:Neoantigen: A Promising Target for the Immunotherapy of Colorectal Cancer.
Neoantigen: A Promising Target for the Immunotherapy of Colorectal Cancer.
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目前,结直肠癌的治疗策略多种多样,包括手术、化疗、放疗和靶向治疗。近年来,随着免疫治疗的不断发展,免疫检查点抑制剂(ICIs)能够显著改善微卫星高度不稳定的晚期结直肠癌患者的治疗。除ICIs外,新抗原作为一类肿瘤特异性抗原(TSA),被视为多种癌种的新型免疫治疗靶点,并正在探索用于抗肿瘤治疗。基于新抗原的免疫治疗策略包括肿瘤疫苗和过继细胞治疗(ACT)。这些方法旨在通过增强宿主T细胞对新抗原的免疫应答来消除肿瘤细胞。此外,对于MSS结直肠癌,这种突变率低、微卫星稳定的“冷肿瘤”对ICIs不敏感,而新抗原可能提供一条有前景的免疫治疗途径。在本综述中,我们总结了结直肠癌新抗原预测的现状以及当前新抗原的临床试验,并讨论了基于新抗原的疗法用于治疗CRC的困难和局限性。
At present, there are various treatment strategies for colorectal cancer, including surgery, chemotherapy, radiotherapy, and targeted therapy. In recent years, with the continuous development of immunotherapy, immune checkpoint inhibitors (ICIs) can significantly improve the treatment of advanced colorectal cancer patients with high levels of microsatellite instability.
In addition to ICIs, neoantigens, as a class of tumor-specific antigens (TSA), are regarded as new immunotherapy targets for many cancer species and are being explored for antitumor therapy. Immunotherapy strategies based on neoantigens include tumor vaccines and adoptive cell therapy (ACT). These methods aim to eliminate tumor cells by enhancing the immune response of host T-cells to neoantigens.
In addition, for MSS colorectal cancer, such "cold tumors" with low mutation rates and stable microsatellites are not sensitive to ICIs, whereas neoantigens could provide a promising immunotherapeutic avenue. In this review, we summarized the current status of colorectal cancer neoantigen prediction and current clinical trials of neoantigens and discussed the difficulties and limitations of neoantigens-based therapies for the treatment of CRC.
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