Next level SUMO wrestling acquired resistance to immunotherapy of cancer

Despite progress in single-cell RNA sequencing, our understanding of the complex interplay between the tumour infiltrating immune system and cancer cells is limited due to a limited understanding of the changes in membrane proteins of immune cells and cancer cells during immunotherapy. Changes at RNA levels don’t directly translate to changes in membrane expression of proteins due to tight control of membrane protein expression by the ubiquitin-proteasome system. Examples are proteins such as MHCII and CD86 that are efficiently degraded by the ubiquitin-proteasome system. With the latest developments in single cell proteomics it is now possible to directly measure changes in the proteome with single cell resolution. Although this offers deep insights into the regulation of cellular processes in each cell a significant part of the recognition of tumor cells occurs on the cell surface. The current method of choice for the analysis of cell surface markers of single cells is FACS analysis although the number of proteins, which can be followed is limited to less than 30.
Lastest research showed that the inhibition of the SUMO modification pathway can change the surface expression of many proteins and thus modulating the recognition of treated cells by the immune system. In this project we will develop a new branch of mass-spectrometry-based single cell proteomics which will allow us to target only the surface of cells to characterize the heterogeneity of the cancer cell population on a single cell level. We will apply this technology to the biological question of how SUMOylation inhibition changes the surface proteome on single cell level and thus deepen our understanding on how we can utilize this for the development of new cancer treatments.