The Role of Biomarkers for the Prediction of Response to Checkpoint Immunotherapy and the Rationale for the Use of Checkpoint Immunotherapy in Cervical Cancer
The Role of Biomarkers for the Prediction of Response to Checkpoint Immunotherapy and the Rationale for the Use of Checkpoint Immunotherapy in Cervical Cancer
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DOI：
10.1016/j.clon.2019.07.003
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发表时间：
2019-12-01
影响因子：
3.4
通讯作者：
Michael, A.
中科院分区：
文献类型：
--
作者：
Otter, S. J.;Chatterjee, J.;Michael, A.
检查点免疫疗法彻底改变了黑色素瘤的治疗方式，并且在肺癌、膀胱癌、肾癌和头颈癌方面也显示出显着的疗效。目前，宫颈癌检查点免疫疗法的试验还处于早期阶段，但将其作为一种治疗选择有很好的理由，特别是因为宫颈癌是一种病毒驱动的癌症，因此应该被免疫系统识别为外来癌症。本综述探讨了选择其他癌症免疫治疗患者的生物标志物，例如程序性死亡配体 1 (PD-L1) 表达、肿瘤浸润淋巴细胞和总突变负荷，并将这些生物标志物与宫颈癌联系起来。对以“免疫疗法”或“宫颈癌”或“检查点封锁”或“肿瘤浸润淋巴细胞”或“总突变负担”为术语的英文出版物进行了 PubMed 检索。包含符合这些标准且 2018 年 10 月 8 日之前在 PubMed 上可用的文章。结果显示，高达 90% 的宫颈癌中 PD-L1 呈阳性，总突变负荷中等偏高，每兆碱基有 5-6 个突变。此外，宫颈癌的肿瘤微环境对预后也有影响，CD8+肿瘤浸润淋巴细胞与CD4+T调节细胞的较高比例与生存率的提高有关。迄今为止的临床研究表明，宫颈癌对检查点免疫疗法的缓解率为 10-25%。宫颈癌表现出许多已被证明与其他肿瘤部位对检查点免疫治疗的反应相关的特征。然而，迄今为止的回复率在 10-25% 左右。因此，可能需要将免疫治疗药物或检查点抑制剂与放射治疗相结合，以最大限度地发挥利用宿主免疫系统对抗癌症的治疗效果。 (C) 2019 年皇家放射科医生学院。由爱思唯尔有限公司出版
Checkpoint immunotherapy has revolutionised the way that melanoma is treated and has also shown significant effectiveness in lung, bladder, renal, and head and neck cancers. At the present time, trials of checkpoint immunotherapy in cervical cancer are at early phases, but there is very good rationale for pursuing this as a treatment option, especially as cervical cancer is a virally driven cancer and therefore should be recognised by the immune system as being foreign. This review explores the biomarkers for the selection of patients for immunotherapy in other cancers, such as programmed death ligand 1 (PD-L1) expression, tumour infiltrating lymphocytes and total mutational burden, and relates these biomarkers to cervical cancer. A PubMed search was carried out for publications published in English with the terms 'immunotherapy' OR 'cervical cancer' OR 'checkpoint blockade' OR 'tumour infiltrating lymphocytes' OR 'total mutational burden'. Articles that met these criteria and were available on PubMed before 8 October 2018 were included. The results showed that PD-L1 is positive in up to 90% of cervical cancers and that the total mutational burden is moderately high, with 5-6 mutations per megabase. In addition, the tumour microenvironment in cervical cancer has an impact on prognosis, with higher ratios of CD8+ tumour infiltrating lymphocytes to CD4+ T regulatory cells being associated with improved survival. Clinical studies to date have shown the response rate of cervical cancer to checkpoint immunotherapy to be in the region to 10-25%. Cervical cancer exhibits many of the features that have been shown to be correlated with response to checkpoint immunotherapy in other tumour sites. However, response rates to date are in the region of 10-25%. Therefore, combinations of immunotherapeutic agents or checkpoint inhibitors with radiotherapy may be required to maximise the therapeutic benefit of harnessing the host immune system to fight cancer. (C) 2019 The Royal College of Radiologists. Published by Elsevier Ltd.