Lung cancer is the leading cause of cancer death in the world. Currently, surgical resection is the most suitable treatment for patients with early-stage non-small cell lung cancer (NSCLC). However, recurrence is very frequent. Tumour immune infiltration has been correlated with patient outcome; therefore, a better understanding of the tumour immune microenvironment (TME) would provide critical information for the development of novel therapeutic approaches.
We aim to correlate spatial characteristics of the immune microenvironment with patient outcome and study how the microenvironment influences the evolution of the disease to identify new predictive biomarkers and propose therapeutic strategies for the two main subtypes of NSCLC: squamous cell carcinoma (LUSC) and adenocarcinoma (LUAD).
This project is using emerging methodologies on paraffin-embedded tissue sections: the MIBIscope that enables single cell spatial proteomics; and the GeoMX that allows quantification of the entire transcriptome for in situ spatial transcriptomic analysis.
We stained 94 tissues of early-stage surgically resected NSCLC with a purpose-developed 38-antibody panel for MIBI. We observed that macrophages and CD8 T cells were present in higher proportion within the tumour compared with the surrounding stroma, highlighting the importance of spatial analysis. When comparing clinical outcomes, we saw a significant increase in the percentage of granulocytes in the TME of short survival patients with LUSC (<3yrs) compared with long survival patients (>6yrs). In LUAD, we detected an increase in CD4 T cells infiltrating the tumour of long survivors compared with short survivors. We are now characterising these populations and studying in detail their spatial relationships. We are also exploring how transcriptional differences between the survival outcomes can relate to the immune infiltrate obtained from the spatial proteomic analysis.
Combined, these technologies will provide in depth analysis of the localisation, the activation status and the interaction of immune cell types and their local impact on tumour cell characteristics and evolution.