Hematologic Oncology Update, Issue 1, 2016 (Video Program)Correlation between PD-L1 expression and response to anti-PD-1 antibodies in HL
1:57 minutes.
TRANSCRIPTION:
DR YOUNES: The Hodgkin lymphoma treatment with PD-1 antibodies came late to the game. So we’re learning from the solid-tumor experience in terms of what predicts response and resistance to PD-1 antibodies. So what we know so far, the higher the level of PD-L1 on tumor cells or PD-1 on T lymphocytes, the higher the response rate. Again, these are not black and white but in general. The higher the number of T cells in the microenvironment, especially those that express PD-1, the higher the response rate to PD-1 antibodies. And Hodgkin lymphoma meets those 2 criteria. There’s a lot of PD-1/PD-L1 expressed on the Reed-Sternberg cells, and there’s tons of T cells in the microenvironment. DR LOVE: And there’s also some specific amplification that is thought to relate to this? DR YOUNES: Right. So this is a genetic explanation for why Reed-Sternberg cells express high levels of PD-1/PD-L1. There is genetic amplification of PD-1/PD-L1 genes, which are located in 9p24.1 amplicon in Hodgkin disease patients. The same amplicon also has the gene for JAK2. And JAK2 also can indirectly increase the expression of PD-1, so the genetic explanation for why Reed-Sternberg cells have high levels of PD-1/PD-L1. DR LOVE: Do you think there’s any way, in your own mind, you can correlate what we see and what we’ve known histologically when you see Reed-Sternberg cells isolated in a sea of immunologic cells? I guess the thinking is those cells are there but are not active? DR YOUNES: That’s right. What we’ve learned now, at least from the PD-1 experience, these T cells, although what may have looked as immune incompetent, we know now that they’re immune reprogrammable. So they can reprogram to become killer cells, which is really nice to know. We never knew that before. |