Immune-checkpoint therapy in non-small cell lung carcinoma:molecular characterisation of tumour microenvironment to improve anti-PD1/PD-L1 drug class.

在全球范围内，肺癌导致的死亡人数比其他任何癌症都多，而且已经在大多数确诊患者身上扩散，对他们来说，疗效有限的化疗一直是唯一可用的治疗方法。幸运的是，最近研制出了一种新的“免疫调节药物”。这些药物通过去除肿瘤形成的防御系统来保护它免受人体正常免疫系统的攻击，使其暴露在人体免疫细胞的攻击之下。目前预测这些药物是否有效的唯一手段是评估肿瘤细胞上一种名为PD-L1的蛋白质的数量。不幸的是，这种特殊的生物标记物缺乏准确性；一些应该有反应的患者没有反应，而一些几乎没有PD-L1的患者可能会有反应，但却错过了这种治疗。我们的研究将通过观察PD-L1在肿瘤不同部分和肿瘤扩散区域之间的差异，它与炎症和基因突变的关系，以及所有这些之间的相互关系，来研究PD-L1缺乏精确度的原因。最终，我们希望提高判断肺癌患者个体是否对这些药物有反应的准确性，以便以有效和成本效益的方式提供最有益的治疗。

Lung cancer kills more people worldwide than any other cancer and has already spread in most patients at diagnosis, for whom chemotherapy of limited effectiveness has been the only treatment available. Fortunately, a new class of 'immune modulating drugs' has been recently developed. These work by removing the defences the tumour develops to protect it from the body's normal immune system, exposing it to attack by the body's immune cells.The only means currently to predict whether these drugs will work is to assess the amount of a protein called PD-L1 on the tumour cells. Unfortunately, this particular 'biomarker' lacks accuracy; some patients who should respond do not and some patients who have little/no PD-L1 would probably respond but are missing out on this treatment. Our study will examine why PD-L1 lacks precision by looking at how it varies between different parts of the tumour and areas of tumour spread, how it relates to inflammation and genetic mutations, and how all of these inter-relate. Ultimately, we wish to improve the accuracy of determining whether an individual patient with lung cancer will respond to these drugs, so that the most beneficial treatment can be given in an efficient and cost-effective manner.