The Immune Microenvironment of the Hydatidiform Mole and Invasive Mole

Author(s): Yiqun Yang, Jia Wei, Xiaoxue Zhang, Juncheng Wei


To investigate the expression profiles of the cytotoxic T-lymphocyte protein 4 (CTLA-4), programmed cell death protein 1(PD-1), programmed cell death-Ligand 1(PD-L1), Twist1, Ki-67, CD4, CD8 and CD11b in hydatidiform mole (HM) and invasive mole (IM).


In this study, 19 cases of complete hydatidiform mole (CHM), 9 cases of partial hydatidiform mole (PHM) and 10 cases of IM were selected based on histopathological criteria. All cases were confirmed by the P57 immunohistochemistry (IHC). The expression of CTLA-4, PD-1, PD-L1, Twist1, Ki-67, CD4, CD8 and CD11b were detected by IHC using paraffin-embedded tissue sections. Expression level of these markers was scored semi-quantitatively according to the staining intensity, percentage of positive cells and immunoreactivity score (IRS).


As for HM, CD11b staining in decidual cells were predominant, followed by CD4+ cells, PD-L1+ cells, Ki-67+ cells, CTLA-4+ cells and CD8+ cells. PD-L1+ cells were present in 14/15 cases. In the villi, the major immune cells were PD-L1+ cells, followed by Ki-67+ cells. Noteworthy, CTLA-4 and CD8 did not express in the villi. Specifically, in the decidual compartment, Twist1 expression was stronger in PHM compared with CHM (p=0.039). While in the villi, Ki-67 was significantly expressed in CHM compared with PHM (p=0.0175). PD-L1 and CD4 immunostaining were higher in PHM than CHM (p=0.0153 and p=0.0127, respectively). In addition, HM has an increased IRS of PD-1, PD-L1, Ki-67and CD11b compared with IM.


This study demonstrated that PD-1/PD-L1 and CTLA-4 pathways collectively contribute to the immune tolerance of GTD and evidenced that a more prominent immunosuppressive microenvironment is present in PHM than CHM.

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