Increase in PD-L1 expression after pre-operative radiotherapy for soft tissue sarcoma

Area of Science:

• Oncology
• Immunology
• Radiotherapy

Background:

• Soft tissue sarcomas (STS) typically show minimal programmed death-ligand 1 (PD-L1) expression, limiting efficacy of PD-1/PD-L1 targeted therapies.
• Pre-clinical studies suggest radiotherapy (RT) can enhance PD-L1 expression.

Purpose of the Study:

• To investigate the effect of pre-operative RT on PD-L1 expression in STS tumors and tumor-associated macrophages (TAM).
• To evaluate the correlation between post-RT PD-L1 expression and distant metastasis (DM) rates in STS patients.

Main Methods:

• Immunohistochemistry was used to assess PD-L1 expression on tumor cells and TAMs in biopsy and resection samples from 46 STS patients treated with pre-operative RT.
• PD-L1 expression was compared pre- and post-RT, with a control group of 5 patients not receiving RT.
• Kaplan-Meier statistics and multivariate analyses were employed to correlate PD-L1 expression with DM rates.

Main Results:

• No STS patients showed PD-L1 tumor expression pre-RT; 10.9% showed expression post-RT (p=0.056).
• PD-L1 expression on TAMs significantly increased post-RT (15.2% to 45.7%, p=0.003).
• Patients with post-RT PD-L1 TAM expression had significantly lower 3-year freedom from DM (49.7% vs. 87.8%, p=0.006) and PD-L1 TAM positivity was an independent predictor for DM (HR=0.16, p=0.042).

Conclusions:

• Pre-operative RT can induce PD-L1 expression in STS tumors and TAMs.
• Elevated PD-L1 expression on TAMs post-RT is associated with an increased risk of distant metastases in STS patients.