Commentary on Mascaux et al. , Immune Evasion before Tumour Invasion in Early Lung Squamous Carcinogenesis. Nature. 2019;571:570-5

Abstract

Cancer biology has long been characterised by definitive hallmarks [1,2]; acquired traits that inevitably footprint the mutational history of its transformation. It is only recently that molecular profiling techniques have offered us the opportunity to chart the sequence of these mutations—allowing us to perceive these traits, not simply as hallmarks, but as milestones in the evolution of cancer. Squamous cell carcinoma of the lung accounts for approximately 30 percent of lung cancers and remains a world-wide health problem. Mascaux et al. [3] contribute to our growing understanding of carcinogenesis by demonstrating the crucial role of immune evasion in the pre-invasive stages of squamous cell carcinoma of the lung, building on previous studies implying that a breakdown in immune surveillance underpins this process [4,5]. Key to their report is the temporal information gleaned by analysing 9 distinct morphological stages in the development of this disease; from which arises the suggestion that escape from host immunity occurs prior to the cancer’s capability to metastasise. Crucially, the directionality of this sequence may have important implications for detection and early prevention of lung cancer—a condition which remains largely incurable because of its presentation mainly at advanced stages. This comes at an opportune moment in efforts centred on early detection. In terms of macroscopic disease, the NELSON trial is a randomised, controlled population-based screening study exploring volume computed-tomography in at-risk groups for lung cancer. Recently, the investigators reported a 26% reduction in lung cancer mortality in men and 39%–61% in women at 10 years of follow-up [6]—a clear indication that targeted screening is of substantial benefit. Such are the implications, that the United Kingdom National Health Service has recently invested Open Access