Surgical resection is, and has been for centuries, the front-line approach for treating cancer. However, it is often not possible to remove the entire tumour, resulting in cancerous cells remaining behind in the wound bed. A cancer prone to relapse is sarcoma; a group of aggressive cancers derived from muscle, fat or connective tissues. Despite intensive treatment with chemotherapy, relapses occur in approximately half of the patients with sarcoma, and two in three patients with relapse will die of their disease within 5 years.
Although surgery is the mainstay treatment in nearly all cancers, it is currently not well understood how the wound healing response impacts cancer growth and the local immune microenvironment. To develop effective new treatments to prevent relapse after surgery I have been investigating how surgery impacts the tumour and the local anti-tumour immune response over time. The surgical wound healing environment has many factors to consider; how the wound healing response changes over time, the influx and roles of different immune cells, the response of the cancer cells and associated cells, and the location of immune cells in proximity to the remaining cancer cells. Using a model of surgical resection which I developed to mimic residual disease after surgery, we used bulk RNAseq (time-course data), single cell RNAseq (cellular pinpointing) and spatial transcriptomics (spatial location) to map the interaction between the tumour and the wound microenvironment following surgery.
There are benefits and limitations to all 3 transcriptomics methods, but it is only with all 3 combined we have been able to uncover interesting biology. It is with this information we can work with the natural wound healing response to develop future therapies with consideration to the molecular, cellular, temporal and spatial application.