Solid tumors are complex ecosystems, where genetically aberrant malignant cells multiply uncontrolled, stimulate the growth of new blood vessels and remodel the local microenvironment to favour tumor growth, evasion from the immune system and resistance to therapies. Therapeutic targeting of immune inhibitory interactions with the so-called immune checkpoint inhibitors revolutionized the treatment of advanced solid tumors including non-small cell lung cancer and resulted in the award of the 2018 Nobel Prize in Physiology or Medicine to Tasuku Honjo and James Allison. Nevertheless, today only a small fraction of lung cancer patient respond to checkpoint inhibitors. Recent advances in single-cell resolved spatial transcriptomics allow investigating the gene expression and tissue location of thousand of cells in a single experiment, thus providing the unprecedented opportunity to study cell-cell communication between neighboring cells.
In this study, single-cell resolved spatial transcriptomic approaches will be leveraged to dissect the complex interplay between malignant, stromal and immune cells in the tumor microenvironment in non-small cell lung cancer, triple negative breast cancer and childhood neuroblastoma in order to identify recurring interactions that could be targeted therapeutically.