Natural Killer Cells in Paediatric Soft Tissue Sarcomas: A Systematic Review

Paediatric soft tissue sarcomas (pSTS) are a rare and heterogeneous group of malignant tumours arising in tissues of mesenchymal origin. The role of natural killer (NK) cells in pSTS remains poorly understood, with evidence fragmented across small preclinical studies and early-phase clinical trials. We therefore aimed to systematically review preclinical and clinical evidence of NK cell presence, activity, and therapeutic potential in pSTS. This review was conducted in accordance with PRISMA guidelines (PROSPERO Registration Number: CRD420251072481) searching MEDLINE (Ovid), EMBASE (Ovid) and Web of Science. Preclinical studies indicated that several pSTS subtypes, including rhabdomyosarcoma (RMS) and non-RMS soft tissue sarcomas (NRSTS), are susceptible to NK cell-mediated lysis. Cytokine activation and sensitising agents can be used to improve NK cell-mediated killing against pSTS cells in vitro. CAR-NK cells have also demonstrated potent cytotoxicity against RMS specifically in vitro and in vivo. Clinical trials assessing adoptive transfer of NK cells into pSTS patients are ongoing. In conclusion, NK cells demonstrate encouraging preclinical activity in pSTS, although the available evidence for this is largely dominated by studies in RMS. However, there is a need for further research in both RMS and NRSTS to allow for translation into meaningful clinical benefit.