Hepatocellular Carcinoma Update, Issue 1, 2017 (Video Program)Biologic rationale for the investigation of immune checkpoint inhibitors for HCC
1:53 minutes.
TRANSCRIPTION:
DR LOVE: Can you talk a little bit about biologically or immunologically why HCC might or might not respond to immune therapy, specifically checkpoint inhibitors? One of the things you hear across different tumors is mutational load. When you think about HCC, you would think — I would have thought there was a high mutational load. But, anyhow, I understand there isn’t. You tell me. Why do you think they respond? DR EL-KHOUEIRY: The short answer is, we do not know. There are many theories as to why HCC may be responding. We know that in the setting of hepatocellular carcinoma, there are many immunosuppressive mechanisms that are turned on, right? There is an increase in immunosuppressive cytokines. There is an increase in myeloid-derived suppressor cells, for example, which counteract the antitumor immunity. There is upregulation of PD-1, PD-L1, PD-L2. There is an upregulation of Tregs, T-regulatory lymphocytes, which are not the ones that will achieve antitumor immunity. So we know that the tumor itself, and potentially the host, are revving up these immunosuppressive mechanisms. And this is why, potentially, using checkpoint inhibition to relieve some of this immunosuppression may be effective in this disease. The other thing is that this is thought to be an inflammatory tumor, right? Most of the time it arises in the setting of an inflammatory etiology, whether it’s viral hepatitis or immune hepatitis, et cetera. So there is an inflammatory background, which, again, may be conducive to immunotherapy. |