Expression of the immune targets in tumor-infiltrating immunocytes of gestational trophoblastic neoplasia

Abstract

Objectives: To evaluate the expression of emerging immune targets in the tumor-infiltrating immunocytes (TIIs) of human gestational trophoblastic neoplasia (GTN) specimens, and to analyze the correlation between the expression patterns and prognosis of GTN patients.Methods: Between January 2008 and December 2017, patients who were diagnosed histologically with GTN were included in this study. The expression densities of LAG-3, TIM-3, GAL-9, PD-1, CD68, CD8, and FOXP3 in the TIIs were assessed independently by two pathologists blinded to clinical outcomes. The expression patterns and correlation with patient outcomes were analyzed to identify prognostic factors.Results: We identified 108 patients with GTN, including 67 with choriocarcinoma, 32 with placental site trophoblastic tumor (PSTT), and 9 with epithelioid trophoblastic tumor (ETT). Almost all GTN patients showed expression of GAL-9, TIM-3, and PD-1 in TIIs (100%, 92.6%, and 90.7%, respectively); LAG-3 was expressed in 77.8% of the samples. The expression densities of CD68 and GAL-9 were significantly higher in choriocarcinoma than that in PSTT and ETT. The TIM-3 expression density in choriocarcinoma was higher than that in PSTT. In addition, the expression density of LAG-3 in the TIIs of choriocarcinoma and PSTT was higher than that in ETT. There was no statistical difference in the expression pattern of PD-1 among different pathological subtypes. The positive expression of LAG-3 in tumor TIIs was a prognostic factor for disease recurrence, and patients with positive expression of LAG-3 in the TIIs had poorer disease-free survival (p = 0.026).Conclusion: Our study evaluated the expression of immune targets PD-1, TIM-3, LAG-3, and GAL-9 in the TIIs of GTN patients and found that they were widely expressed but not associated with patients’ prognoses, excepting the positive expression of LAG-3 was a prognostic factor for disease recurrence.

Intracardiac metastasis of gestational choriocarcinoma: a case report and literature review

“…Thought the current case did not received immunotherapy, and there is no report of patients with GTN and intracardiac metastasis who experience PD-1 and PD-L1 inhibitor, immunotherapy in GTN has made great progress in recent years, with successful therapeutic outcomes in several clinical studies [ 26 – 29 ]. Previous researches have revealed that programmed cell death ligand (PD-L1) is highly expressed in GTN tumor tissue [ 30 , 31 ], and other immune targets TIM-3, LAG-3, and GAL-9 are also widely expressed in GTN [ 32 ]. The CAP-01 clinical trial confirmed the efficiency and safety of PD-1 inhibitor in patients with chemo-refractory and relapsed CTN, and showed a 55% of objective response rate [ 28 ].…”

Epithelioid trophoblastic tumor with lung metastasis: A case report and literature review

“…[3,10,11,49,[53][54][55][56][57] Besides, Yang et al suggested that the positive expression of LAG-3 was a prognostic factor for disease recurrence. [58] But the timing, type and duration of multi-agent chemotherapy are unclear. Zhang et al reported that serum β-hCG is not the only factor of chemotherapy withdrawal and follow-up monitoring, and imaging examination are more essential for ETT.…”

“…[91,93] Since a significant amount of gestational trophoblastic tumors, including ETT, express the PD-L1 receptor, there has been reported immunotherapy using pembrolizumab as a successful treatment in ETT. [13,42,52,58,84] Pembrolizumab has been hypothesized to be a reasonable option for therapy of ETT patients with significant PD-L1 positivity and especially chemo-resistance or recurrent. Additionally, EGFR, VEGF, PD-L2, B7-H3, VISTA, LPCAT1, and CD105 were identified as potential therapeutic targets for metastatic or recurrent ETT.…”