Poster Presentation Multi-Omics Inaugural Conference 2022

Studying the immune microenvironment in lung cancer patients using spatial multi-omic approaches. (#112)

Claire Marceaux 1 2 , Kenta Yokote 1 , Velimir Gayevskiy 1 , Nina Tubau 1 , Daniel Batey 1 , Clare Weeden 1 2 , Terry Speed 1 2 , Kelly Rogers 1 , Marie-Liesse Asselin-Labat 1 2
  1. Walter and Eliza Hall Institute of Medical Research, Parkville, VIC, Australia
  2. University of Melbourne, Melbourne

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 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 NSCLC.

This project is using emerging methodologies on paraffin-embedded tissue sections: the MIBIscope that enables multiplex imaging at single cell resolution using heavy metal-conjugated antibodies bound to the tissue and detected by mass spectrometry-time-of-flight (1); and the GeoMX that allows quantification of the entire transcriptome in selected areas of interest for in situ spatial transcriptomic analysis (2).

We have developed a 38-antibody panel to study the immune cell infiltration with MIBI. We have performed spatial proteomics and transcriptomics analysis of 94 tissues of NSCLC patients for which we possess survival and smoking status. Our first results confirm the importance of the spatial context with specific lymphoid cells infiltrating the tumour of patients with long survival post-surgery (>6yrs) and specific myeloid cells inside the tumour of short survival post-surgery patients (<3yrs). 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 activation status of immune cell types and their local impact on tumour cell characteristics and evolution.

  1. Ptacek, J. et al. Multiplexed ion beam imaging (MIBI) for characterization of the tumor microenvironment across tumor types. Lab. Invest. 1–13 (2020).
  2. Brady L, Kriner M, Coleman I, et al. Inter- and intra-tumor heterogeneity of metastatic prostate cancer determined by digital spatial gene expression profiling. Nat Commun. 2021;12(1):1426.