In summary, this study revealed that the upregulated expression of LCK might not only induce the polarization of tumor-associated macrophages toward the M1 type via the ‘LCK-INF-γ/IL-12-TNF/PI3K-NF-κB’ axis but also improve the secretion of CXCL9, 10, and 11 in STS microenvironments, which work together to improve the overall response rate and prognosis of STS patients. Here, PIK3CD is linked to neoplasm.