| 权 阳,赵 征,姚俊涛.非小细胞肺癌免疫治疗预测标志物研究进展[J].肿瘤学杂志,2019,25(11):952-956. |
| 非小细胞肺癌免疫治疗预测标志物研究进展 |
| Progress on Predictive Markers of Immunotherapy for Non-small Cell Lung Cancer |
| 投稿时间：2019-05-05 |
| DOI：10.11735/j.issn.1671-170X.2019.11.B005 |
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| 中文关键词: 非小细胞肺癌 免疫治疗 预测标志物 PD-L1 肿瘤突变负荷 MSI TIL |
| 英文关键词:non-small cell lung cancer immunotherapy predictors PD-L1 tumor mutation burden MSI TIL |
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| 摘要点击次数: 1758 |
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| 中文摘要: |
| 摘 要：目前免疫检查点抑制剂在肺癌治疗方面取得了突破性进展，正在迅速的改变着肺癌的治疗模式。由于免疫治疗费用高昂，单药治疗的获益人群较低，且非筛选人群免疫治疗的获益率仅为20%，因此如何筛选出免疫治疗获益人群显得尤为重要。肿瘤通过PD-1/PD-L1通路发生免疫逃逸，在效应CD8+ T细胞进入肿瘤细胞周围过程中，产生大量IFNγ，可以诱导肿瘤细胞表面PD-L1上调，与效应T细胞表面的PD-1受体结合，从而降低效应T细胞的增殖，诱导其凋亡，引起细胞毒T细胞的耗竭，通过上调PD-L1的表达下调效应T淋巴细胞的抗肿瘤免疫反应，创造出适合自身生长的局部微环境，形成免疫逃逸，促进肿瘤细胞的生长。肿瘤突变负荷已被多个临床研究证实可作为一种免疫治疗预测标志物，其表达高低可能与吸烟具有一定的相关性。微卫星不稳定在肺癌中表达较低，是否可将其与肿瘤淋巴浸润联合作为预测免疫治疗的标志物有待证实。除此之外，T细胞受体多样性、主要组织相容性复合体1分子的表达均可能影响肿瘤新抗原的呈递和识别。DNA损伤修复基因的异常发生功能性突变，导致其他驱动基因缺失和插入性突变增加，这些移码突变导致新抗原和肿瘤突变负荷增加，与免疫检查点抑制剂的疗效相关。免疫治疗时代的开展推动了对免疫治疗预测标志物更加严格的要求，新的免疫预测标志物层出不穷，免疫时代赋予非小细胞肺癌免疫治疗的预测标志物更需要临床进一步证实。 |
| 英文摘要: |
| Abstract：Immunocheckpoint inhibitors have made breakthrough in the treatment of lung cancer and changed its therapeutic mode. Currently，the benefit rate of single immunotherapy drug in non-screened patients is only 20%，so how to screen out the benefit population for immunotherapy is particularly important. Tumor by PD-1/PD-L1(programmed cell death 1 / programmed cell death 1 ligand 1) pathways in the immune escape，in effect in the process of CD8+ T cells into the surrounding tumor cells and produce a large number of IFN gamma，PD can induce the tumor cell surface-L1 increases，and the effect of T cell receptors on the surface of PD-1，thus reducing effect of T cell proliferation and induce its apoptosis，causes the cytotoxic T cell depletion. By up-regulating the expression of pd-l1 and down-regulating the anti-tumor immune response of T lymphocytes，local microenvironment suitable for their own growth is created to form immune escape and promote the growth of tumor cells. TMB(tumor mutation burden) has been confirmed by multiple clinical studies as a predictive marker of immunotherapy，and its expression level may be correlated with smoking. MSI(microsatellite instability，microsatellite instability) expressed in lung cancer is low，and whether it can be with TIL(tumor infiltrates lymphocytes and tumor lymphatic invasion) joint as a biomarker for predicting immunotherapy needs to be confirmed. In addition，the diversity of TCR(T-cell receptor(T cell receptor) and the expression of MHC-1(major histocompatibility complex 1，major histocompatibility complex 1) molecules may affect the presentation and recognition of tumor new antigens. Abnormal functional mutations of DNA damage repair genes lead to the deletion of other driver genes and the increase of insertional mutations. These code shift mutations lead to the increase of neoantigen and tumor mutation load，which is related to the efficacy of immune checkpoint inhibitors. The development of the era of immunotherapy has promoted more stringent requirements on immunotherapy predictive markers，and new immunoprediction markers are emerging in an endless stream. |
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