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Membranous and Cytoplasmic Expression of PD-L1 in Ovarian Cancer Cells

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eMediNexus    26 October 2017

A new study published in Cell Physiology and Biochemistry investigated the role of intracellular or cytoplasmic programmed death ligand 1 PD L1 in ovarian cancer cells. In this study flow cytometry FCM real time PCR qPCR immunohistochemistry IHC and western blot were employed to determine the expression of PD L1 in ovarian cancer cells. The cytokines detected in the tumor or tumor associated macrophage TAM were used to treat cancer cells. The results revealed that PD L1 was variably expressed in the cytoplasm and the cell surface of both HO8910 and SKOV3 cells human ovarian carcinoma cells . TAM or interferon gamma IFN 947 tumor necrosis factor TNF 945 interleukin IL 10 and IL 6 released from TAM stimulated the expression of PD L1 at the surface of the cancer cells. The IHC results were consistent with the data in vitro showing infiltration of TAM correlated with membranous PD L1. The increases of PD L1 at the surface were due to the contribution of extracellular signal regulated kinase ERK 1 2 and phosphoinositide 3 kinase PI3K pathway activation. Therefore inducible membranous PD L1 expression on SKOV3 inhibited CD8 cluster of differentiation 8 T cell function and cytoplasmic PD L1 promoted cancer cell growth. Furthermore in mouse models both PD L1 and PD 1 monoclonal antibody mAb resulted in tumor growth inhibition and demonstrated a potential to decrease the number of PD 1 CD8 T cells. Hence it was concluded that TAM induced PD L1 on the cancer cells represents an immune evasion mechanism. It was stated that these findings confirmed the therapeutic potential of PD L1 PD 1 mAb to reactivate anti tumor immunity in ovarian cancer.

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