Despite aggressive surgery,
chemotherapy, and
radiotherapy, survival of children and adolescents and young adults (AYAs) with
sarcoma has not improved significantly in the past four decades.
Immune checkpoint inhibitors (ICIs) are an exciting type of
immunotherapy that offer new opportunities for the treatment of paediatric and AYA
sarcomas. However, to date, most children do not derive a benefit from this type of treatment as a monotherapy. The immunosuppressive tumour microenvironment is a major barrier limiting their efficacy. Combinations of ICIs, such as anti-PD-1
therapy, with
targeted molecular therapies that have immunomodulatory properties may be the key to breaking through immunosuppressive barriers and improving patient outcomes. Preclinical studies have indicated that several
receptor tyrosine kinase inhibitors (RTKi) can alter the tumour microenvironment and boost the efficacy of anti-PD-1
therapy. A number of these combinations have entered phase-1/2 clinical trials, mostly in adults, and in most instances have shown efficacy with manageable side-effects. In this review, we discuss the status of ICI
therapy in paediatric and AYA
sarcomas and the rationale for co-treatment with RTKis. We highlight new opportunities for the integration of ICI
therapy with RTK inhibitors, to improve outcomes for children with
sarcoma.