Promising clinical trials targeting mast cells and TAMs, [(pexidartinib: KIT, CSF1R, and FLT3 inhibitor + sirolimus, an mTOR inhibitor) (NCT02584647)], underscore the potential for combination strategies, yet the immunosuppressive TME and variable response to PD-1/PD-L1 blockade, highlight the need for predictive biomarkers and strategies to augment MPNST immunogenicity. This evidence concerns the gene KIT and malignant peripheral nerve sheath tumor.