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:Immunotherapy for Colorectal Cancer: Mechanisms and Predictive Biomarkers.
Immunotherapy for Colorectal Cancer: Mechanisms and Predictive Biomarkers.
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早期结直肠癌的5年生存率较高,根据具体分期为65%至92%;但癌症转移后,这一比例降至13%。结直肠癌一线治疗(如化疗和放疗)常导致患者出现剂量限制性毒性,并使癌细胞获得耐药。需要更多靶向治疗改善患者结局和生活质量。免疫疗法通过肽、细胞、抗体、病毒或小分子药物激活或训练免疫系统杀伤癌细胞。结直肠癌免疫检查点阻断、过继细胞治疗、单克隆抗体、溶瘤病毒、抗癌疫苗和免疫调节剂的临床前及临床研究已显示前景,但对错配修复功能正常的患者仍存在局限。本文综述结直肠癌免疫治疗的临床前和临床研究,以及预测治疗应答的生物标志物,并探讨尚待解决的问题,包括如何优化联合治疗以最大限度提高疗效、减少毒性并防止获得性耐药,以及如何使错配修复功能正常的患者对免疫治疗增敏。
Though early-stage colorectal cancer has a high 5 year survival rate of 65-92% depending on the specific stage, this probability drops to 13% after the cancer metastasizes. Frontline treatments for colorectal cancer such as chemotherapy and radiation often produce dose-limiting toxicities in patients and acquired resistance in cancer cells. Additional targeted treatments are needed to improve patient outcomes and quality of life. Immunotherapy involves treatment with peptides, cells, antibodies, viruses, or small molecules to engage or train the immune system to kill cancer cells.
Preclinical and clinical investigations of immunotherapy for treatment of colorectal cancer including immune checkpoint blockade, adoptive cell therapy, monoclonal antibodies, oncolytic viruses, anti-cancer vaccines, and immune system modulators have been promising, but demonstrate limitations for patients with proficient mismatch repair enzymes. In this review, we discuss preclinical and clinical studies investigating immunotherapy for treatment of colorectal cancer and predictive biomarkers for response to these treatments.
We also consider open questions including optimal combination treatments to maximize efficacy, minimize toxicity, and prevent acquired resistance and approaches to sensitize mismatch repair-proficient patients to immunotherapy.
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