PVR expression in tumor microenvironment of advanced hepatocellular carcinoma.

Abstract

e16113 Abstract Background: PVR (CD155)/TIGIT signaling has been investigated as a new immune checkpoint target in many cancers, including hepatocellular carcinoma (HCC). However, the expression and clinical significance of PVR, the ligand of TIGIT, have not been explored in the tumor microenvironment (TME) of advanced HCC. Methods: Patients with HCC who had adequate tumor tissues obtained at advanced stage were enrolled in the study. The membranous staining of PVR of tumor tissues, detected by immunohistochemistry (IHC), was semiquantitatively scored as IHC 0, 1, 2, or 3 if < 1%, ≥1% but < 5%, ≥5% but < 10%, or ≥10% of tumor cells (TCs) and tumor-infiltrating immune cells (ICs) were PVR positive. The correlation of PVR expressions and other clinic-pathologic factors was analyzed. Results: Sixty-seven patients were included in the study. Among them, 57 (85.1%) were male, 32 (47.8%) were aged over 60 years, 48 (71.6%) were HBV-reactive, and 23 (34.3%) had been treated with sorafenib before obtaining tumor tissues. Thirteen (19.4%) and 18 (26.9%) tumor samples showed positive PVR expressions in TCs and ICs, respectively (TCs, IHC 1/2/3: 3/3/7; ICs, IHC 1/2/3: 7/3/8). The expressions of PVR in TCs or ICs were not associated with sex, age, HBV/HCV infection, previous sorafenib treatment, or overall survival of the patients. Notably, in both TCs and ICs, the intensities of PVR expression were inversely correlated with PD-L1 expression for patients with at least IHC ≥1 in either PVR or PD-L1 (TCs, n = 26, r = -0.6966, p < 0.0001; ICs, n = 46, r = -0.4548, p = 0.0015). Conclusions: PVR expression can be identified in both TCs and ICs of TME of advanced HCC. The expressions of PVR and PD-L1 were inversely correlated. These findings may provide clinical implications for development of combination immunotherapy in advanced HCC. (This work is supported by grants from the Ministry of Science and Technology, Taiwan, MOST 110-2314-B-002-204-MY3). [Table: see text]