The Role of Natural Killer Cells in Soft Tissue Sarcoma: Prospects for Immunotherapy

SIMPLE SUMMARY: Soft-tissue sarcomas (STS) represent about 80% of sarcomas, and are a heterogeneous group of rare and malignant tumors. Morphological evaluation has been the standard model for the diagnosis of sarcomas, and even in samples with similar characteristics, they present genetic differences, which further increases the diversity of sarcomas. This variety is one of the main challenges for the classification and understanding of STS patterns, as well as for the respective treatments, which further decreases patient survival (<5 years). Natural Killer (NK) cells have a fundamental role in the control and immune surveillance of cancer development, progression and metastases. Notwithstanding the scarcity of studies to characterize NK cells in STS, it is noteworthy that the progression of these malignancies is associated with altered NK cells. These findings support the additional need to explore NK cell-based immunotherapy in STS; some clinical trials, although very tentatively, are already underway. ABSTRACT: Soft-tissue sarcomas (STS) represent about 80% of sarcomas, and are a heterogeneous group of rare and malignant tumors. STS arise from mesenchymal tissues and can grow into structures such as adipose tissue, muscles, nervous tissue and blood vessels. Morphological evaluation has been the standard model for the diagnosis of sarcomas, and even in samples with similar characteristics, they present a diversity in cytogenetic and genetic sequence alterations, which further increases the diversity of sarcomas. This variety is one of the main challenges for the classification and understanding of STS patterns, as well as for their respective treatments, which further decreases patient survival (<5 years). Despite some studies, little is known about the immunological profile of STS. As for the immunological profile of STS in relation to NK cells, there is also a shortage of studies. Observations made in solid tumors show that the infiltration of NK cells in tumors is associated with a good prognosis of the disease. Notwithstanding the scarcity of studies to characterize NK cells, their receptors, and ligands in STS, it is noteworthy that the progression of these malignancies is associated with altered NK phenotypes. Despite the scarcity of information on the function of NK cells, their phenotypes and their regulatory pathways in STS, the findings of this study support the additional need to explore NK cell-based immunotherapy in STS further. Some clinical trials, very tentatively, are already underway. STS clinical trials are still the basis for adoptive NK-cell and cytokine-based therapy.