Abstract Systemic relapse, after treatment of a localised primary tumour with neo-adjuvant radiotherapy and surgery, is the major cause of disease related mortality in patients with sarcoma. As with other cancers, many sarcoma patients derive no benefit from anti-PD-1 treatment. Combining radiotherapy and immunotherapy is under investigation as a means to improve response rates and control metastatic disease. Here, we use a retrospective cohort of sarcoma patients, treated with neoadjuvant radiotherapy, and TCGA data to explore patient stratification for immunotherapy and therapeutic targets of relevance to sarcoma. We show a group of patients with immune-hot undifferentiated pleomorphic sarcoma as one of the highest-ranking candidates for emerging 4-1BB targeting agents. A binary hot/cold classification method indicates 4-1BB-high hot sarcomas share many characteristics with immunotherapy responsive cancers of other pathologies. Hot tumours in sarcoma are however substantially less prevalent. Patient stratification, of intense interest for immunotherapies, is therefore even more important in sarcoma.

4-1BB is a target for immunotherapy in patients with undifferentiated pleomorphic sarcoma