Tissue Expression and Plasma Soluble PD-L1 Levels in Patients With Endometrial Cancer

The prognostic role of tissue PD-L1 expression in endometrial cancer (EC) remains controversial. Moreover, its value in guiding anti-PD1/PD-L1 immunotherapy is questionable. The eventual role of soluble PD-L1 (sPD-L1), released by cancer tissue and circulating immune cells, is largely unexplored.

In this pilot study, we investigated the expression of PD-L1 in cancer cells and tumor stroma infiltrating inflammatory cells (TIICs), in parallel with sPD-L1 levels in the plasma of 19 patients with early-stage endometrioid EC, before and after hysterectomy.

Cancer cell membrane staining was noted in 5/19 (26.3%) cases (range=1-5%; median 1% of the cancer cell population). IICs showed positive reactivity in 14/19 (73.7%) cases. sPD-L1 plasma levels ranged from 53-408 pg/ml and 113-557 pg/ml, respectively, in the plasma of patients before and after hysterectomy (p=0.01). High PD-L1 expression by IIC was marginally associated with a high histology grade (p=0.08). High sPD-L1 levels before surgery were significantly associated with ICC PD-L1 expression (p=0.0007), high histology grade (p=0.04), and marginally with T2-stage (p=0.08).

sPD-L1 is easily detectable in the plasma of EC patients and may be associated with aggressive clinical features and PD-L1-expressing immune cells infiltrating the tumor stroma. sPD-L1 plasma levels in EC patients undergoing immunotherapy can be further tested as a biomarker for therapeutic stratification.