St Luke's Cancer Centre, Royal Surrey County Hospital, Guildford, UK; Department of Oncology, Faculty of Health and Medical Sciences, University of Surrey, Guildford, UK.
St Luke's Cancer Centre, Royal Surrey County Hospital, Guildford, UK; Department of Oncology, Faculty of Health and Medical Sciences, University of Surrey, Guildford, UK.
Clin Oncol (R Coll Radiol). 2019 Dec;31(12):834-843. doi: 10.1016/j.clon.2019.07.003. Epub 2019 Jul 19.
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.
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、肾癌和头颈部癌症中也显示出了显著的疗效。目前，宫颈癌检查点免疫疗法的临床试验处于早期阶段，但将其作为一种治疗选择具有非常充分的理由，尤其是因为宫颈癌是一种由病毒驱动的癌症，因此应该被免疫系统识别为外来物。本综述探讨了其他癌症中免疫疗法患者选择的生物标志物，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担，并将这些生物标志物与宫颈癌相关联。在 PubMed 上以“免疫疗法”或“宫颈癌”或“检查点阻断”或“肿瘤浸润淋巴细胞”或“总突变负担”为关键词进行了英文文献检索。符合这些标准且在 2018 年 10 月 8 日前可在 PubMed 上获取的文章被纳入。结果表明，高达 90%的宫颈癌 PD-L1 阳性，总突变负担中等偏高，每个兆碱基有 5-6 个突变。此外，宫颈癌的肿瘤微环境对预后有影响，CD8+肿瘤浸润淋巴细胞与 CD4+调节性 T 细胞的比值较高与生存改善相关。迄今为止的临床研究表明，宫颈癌对检查点免疫疗法的反应率在 10-25%之间。宫颈癌表现出许多与其他肿瘤部位检查点免疫疗法反应相关的特征。然而，到目前为止的反应率在 10-25%之间。因此，可能需要将免疫治疗药物或检查点抑制剂与放疗联合使用，以最大限度地发挥利用宿主免疫系统对抗癌症的治疗益处。
