91P - Erythroid precursor-differentiated myeloid cells promote pulmonary metastasis in hepatocellular carcinoma

Background

Pulmonary metastasis is the most frequently occurring distant metastases of hepatocellular carcinoma (HCC). However, the indicated mechanism of pulmonary metastasis in HCC remains unclarified. Erythroid progenitor-differentiated myeloid cells (EDMCs) were reported to mediate immunosuppression and curtail anti-PD-1/PD-L1 treatment efficacy. The role of EDMCs in the metastasis of HCC and the development of pulmonary metastasis was investigated here.

Methods

The existence of EDMCs in the circulation and spleen of HCC mouse model were validated through Flow Cytometry. EDMCs were sorted using fluorescence-activated cell sorting. CFSE stained EDMCs transfer experiment were conducted to evaluated the Pulmonary metastasis promoting role in HCC mouse model. The transwell migration and invasion experiment of hepa1-6 cells (HCC cell line) cocultured with EDMCs were performed.

Results

Mouse with Pulmonary metastasis of HCC showed higher level of EDMCs in the circulation and spleen than those without Pulmonary metastasis. CFSE EDMCs stained with 5，6- carboxyfluorescein diacetate, succinimidyl ester (CFSE) were detected in the lung of HCC mouse after infusion though caudal vein and those infused mice developed more frequency of pulmonary metastasis than those without EDMCs infusion. IN the coculture experiment EDMCs promoted the migration and invasion of hepa1-6 cells.

Conclusions

EDMCs existed in the circulation of HCC mouse model. EDMCs could migrated from the circulation to the lung of HCC mice. EDMCs could facilitate migration and invasion of hepa1-6 cells migrate and invade. Thus, EDMCs can promote Pulmonary metastasis in Hepatocellular Carcinoma.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

Wei-hang Zhu.

Funding

National Natural Science Foundation of China (81972677, 82103331), Guangdong Basic and Applied Basic Research Foundation (No. 2021A1515011022, 2022A1515010547).

Disclosure

All authors have declared no conflicts of interest.