I am going to try the new PD-L1 inhibitor in vivo experiment.However, when I screened the several murine cancer cell lines in my lab, there is no cell line expressing PD-L1. If I want to use human cancer cell line that express PD-L1 for in vivo tumor model, I should use nude mouse which is eliminated immune response. Would you please suggest other model that I can use human cancer cell for in vivo PD-L1 blocking immune therapy. Thank for all kind of help!
Hi.
I would not recommend test PD-L1 expression in classical established cancer cells lines. The expression of PD-L1 is tightly regulated by the interactions of cancer cells with members of the immune system and with other players in the tumor microenvironment. So you probably don’t detect PD-L1 in your cells because the expression of this molecule would appear as a result of an interaction with other cells. I would recommend you to isolate cancer cells from different mice models and check PD-L1 expression by Facs.
In my opinion your experiment design is not appropriate to test PD-L1 inhibitors. You definitely must do the experiment in mice that have a normal immune system because you expected to block PD-L1 in tumor cells with an blocking antibody and the consequence of this would be that the immune cells T-CD4, T-CD8 increase their activity as a tumoral killing cells. So if you perform your experiment in a NOD SCID mice you probably don’t see any effect of the PD-L1 blockade given the T cell impairment in this kind of mice.
Best.
Previous answer addressed important points. Ultimately, you need to be sure that you're using a sensitive and reliable assay for detecting PD-L1 expression. Flow is fairly reliable at this point. There's considerable variation in the literature on reliability of IHC methods. You certainly want to evaluate PD-L1 expression in tumors and not cell lines since the interaction with the immune system is integral to PD-L1 expression.
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