To study the changes of T cell phenotype, PD-1 (programmed cell death receptor), PD-L1 and immunosuppression-related protein CD73 expression in tumor microenvironment after trans-arterial chemoembolization (TACE) and its value in predicting prognosis.

Hepatocellular carcinoma tissue samples from 20 patients with TACE (T+ group) and 20 without TACE (T- group) prior to surgery were collected from May 2019 to December 2020. We profiled the number of regulatory (FOXP3⁺)Treg, immune-exhausted (CD8⁺/PD-1⁺) T cells and PD-L1, CD73 expression in the tumor by multiple fluorescence immunohistochemistry on tumor tissue sections. We profiled the effects of different T cell phenotypes and CD73 expression levels on progression-free survival. The main factors affecting the prognosis of patients were analyzed by multivariate Cox regression.

The expression level of CD73 in tumor tissues in the T+ group was higher than that in T- group (11.86 vs 7.7, P = 0.047). The numbers of Treg, CD8⁺ and CD8⁺ PD-1⁺ T cells in the T+ group were 35.93, 86.09, and 13.91, which were lower than that in T- group of 60.02 (P = 0.013), 120.27 (P = 0.043), and 28.36 (P = 0.015) ), while the expression level of PD-L1 was not different between T+ group and T- group (23.68 vs 21.04, P = 0.380). The CD73 high expression group showed lower CD8⁺ (84.83 vs 121.53, P = 0.029) and CD8⁺PD-1⁺ (15.00 vs 27.27, P = 0.041) T cell numbers, and there was no difference in the number of FOXP3⁺ between the two groups (45.50 vs 50.45, P = 0.623). Kaplan-Meier survival analysis showed that patients with high CD73 expression and high CD8⁺ PD-1⁺ expression had worse progression free survival (P = 0.009 and 0.019, respectively).

After TACE, the expression of CD73 in the tumor immune microenvironment increased, while the number of FOXP3⁺ and CD8⁺/PD-1⁺ T cells decreased. The high expression of CD73 and the low expression of CD8⁺ PD-1⁺ were related to the poor prognosis of patients, suggesting that targeting CD73 may become a new idea of TACE combination therapy.