Evaluation of PD1 and PD-L1 expression in high-grade sarcomas of the limbs in the adults: possible implications of immunotherapy

Improvement of surgical techniques, associated with the improvement of pre-operative and/or post-operative radiotherapy and chemotherapy, brought enhancements in results in localised cancer in the last 30 years (1). Despite these multimodal therapies, survival rate in non-localised disease did not improve in the last 20 years with high grade of metastasis and local recurrence (2). Metastasis is fatal in most patients with an overall survival (OS) of 12-15 months from diagnosis. Therefore, there is urgency in searching for new treatments instead of conventional therapy (1, 2, 3) and targeted therapies, as monoclonal antibodies and immunotherapy may be an option. Sarcomas were among the first tumours to be considered for manipulation of immune system. Coley reported a case of inoperable small cells sarcoma of the neck in 1891 which completely regressed after a serious episode of erysipelas, associating the response of the immune system to erysipelas to the response of patient tumour (4). Improvements in immunotherapy by transferring cells of adaptive immunity, anti-tumoral vaccines and inhibition of immune checkpoints, allowed a better comprehension of how immune oncology may be applied to treatment of sarcomas (5). Immune checkpoints are cell surface molecules which are endogenous regulators of immune response system and are involved in circumvention mechanism of tumour cell in immune response as well. Programmed cell death receptor 1 (PD-1) is an immune checkpoint receptor expressed on T cells and it is one of inhibitory signals induced during chronic exposition to antigen in external tumour microenvironment which belongs to CD28 family and has a crucial role in tumor immunogenicity. PD-L1 is PD-1 ligand and it is expressed on T cells, B cells, macrophages and dendritic cells (6, 7).