Cancer is a multifactorial trait — undoubtedly with contributions from genes (genetics), epigenetic effects, environmental factors, endogenous influences, and the patient’s changing microbiome. Hence, the relevance of this topic for these GEITP pages. Understanding the biology of carcinogenesis requires deciphering molecular processes in premalignant lesions, and revealing the determinants of the intra-lesional immune reaction during cancer development. The adaptive immune response within tumors has previously been shown to be strongest in the earliest stages of carcinogenesis.
Authors [see attached article] sought to locate, and time, the changes in pre-invasive lesions and their microenvironment during the successive steps in the carcinogenesis of lung squamous cell carcinoma (SCC). Authors demonstrated that immune activation and immune escape occur before tumor invasion; they show relevant immune biomarkers of the pre-invasive stages of carcinogenesis in LUNG. Authors used gene-expression profiling and multispectral imaging to analyze a dataset of nine morphological stages during the development of SCC, which included 122 well-annotated biopsies from 77 patients.
Authors identified evolutionary trajectories of cancer and immune pathways that comprise: [a] a linear increase in proliferation and DNA repair from normal to cancerous tissue; [b] a transitory increase of metabolism and early “immune sensing,” through the activation of resident immune cells, in low-grade pre-invasive lesions; [c] the activation of immune responses and “immune escape” through immune check-points and suppressive interleukins from high-grade pre-invasive lesions; and, ultimately, [d] the activation of the epithelial–mesenchymal transition (EMT) during the invasive stage of cancer.
Authors postulate that carcinogenesis in the lung involves a dynamic co-evolution of pre-invasive bronchial cells and the immune response. These findings highlight the need to develop immune biomarkers for early detection, as well as immunotherapy-based chemopreventive approaches, for individuals who are at high risk of developing lung cancer (e.g. cigarette smokers, uranium mine workers).
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Nature 25 July 2019; 571: 570-575