决定异体 CAR T 细胞排斥与扩增的细胞和分子机制
Cellular and molecular mechanisms determining allogeneic CAR T cell rejection and expansion.
我们评估了11例接受单一批次cemacabtagene ansegedleucel(cema-cel)治疗的大B细胞淋巴瘤患者,cemacabtagene ansegedleucel是一种异体抗CD19 CAR T产品。
英文原题:Non-coding RNAs in cancer immunotherapy: Predictive biomarkers and targets.
本综述总结了在接受不同免疫治疗模式(包括单克隆抗体、小分子抑制剂、癌症疫苗和 CAR-T 细胞)治疗的癌症患者中报道的重要预测性 ncRNA 生物标志物。
背景:由于个体遗传特征、肿瘤微环境复杂性和表观遗传致癌机制存在差异,建立标准化临床预测生物标志物以评估免疫治疗应答仍具挑战。正文:早期监测关键非编码RNA(ncRNA)标志物可能有助于预测癌症免疫治疗的临床疗效,并推动标准化预测标志物的建立。例如,接受抗PD-1治疗的非小细胞肺癌患者血浆miR-125b-5p水平降低与良好结局相关。接受CAR-T 细胞治疗的结直肠癌患者血浆miR-153水平可能反映T细胞杀伤活化情况。miR-148a-3p和miR-375水平可能预测B细胞急性淋巴细胞白血病患者对CAR-T治疗的良好应答。接受GPC3肽疫苗治疗的癌症患者血清miR-1228-5p、miR-193a-5p和miR-375-3p水平被报道为良好应答和总生存改善的预测标志物。因此,亟需进一步研究明确可用于早期预测免疫治疗临床应答的关键ncRNA标志物。结论:本文综述了不同免疫治疗方式(包括单克隆抗体、小分子抑制剂、癌症疫苗和CAR-T细胞)治疗患者中报道的重要预测性ncRNA标志物,并简要探讨未来方向,概述如何优化免疫调节性ncRNA标志物作为预测工具和治疗靶点的技术路径。
BACKGROUND: To date, standardising clinical predictive biomarkers for assessing the response to immunotherapy remains challenging due to variations in personal genetic signatures, tumour microenvironment complexities and epigenetic onco-mechanisms. MAIN BODY: Early monitoring of key non-coding RNA (ncRNA) biomarkers may help in predicting the clinical efficacy of cancer immunotherapy and come up with standard predictive ncRNA biomarkers. For instance, reduced miR-125b-5p level in the plasma of non-small cell lung cancer patients treated with anti-PD-1 predicts a positive outcome. The level of miR-153 in the plasma of colorectal cancer patients treated with chimeric antigen receptor T lymphocyte (CAR-T) cell therapy may indicate the activation of T-cell killing activity. miR-148a-3p and miR-375 levels may forecast favourable responses to CAR-T-cell therapy in B-cell acute lymphoblastic leukaemia. In cancer patients treated with the GPC3 peptide vaccine, serum levels of miR-1228-5p, miR-193a-5p and miR-375-3p were reported as predictive biomarkers of good response and improved overall survival. Therefore, there is a critical need for further studies to elaborate on the key ncRNA biomarkers that have the potential to predict early clinical responses to immunotherapy. CONCLUSION: This review summarises important predictive ncRNA biomarkers that were reported in cancer patients treated with different immunotherapeutic modalities, including monoclonal antibodies, small molecule inhibitors, cancer vaccines and CAR-T cells. In addition, a concise discussion on forthcoming perspectives is provided, outlining technical approaches for the optimal utilisation of immunomodulatory ncRNA biomarkers as predictive tools and therapeutic targets.
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