Stephen M. Ansell, MD, PhD
Immune evasion is one of the biggest obstacles plaguing the implementation of checkpoint inhibitors into the treatment landscape of Hodgkin lymphoma, according to Stephen M. Ansell, MD, PhD.
at the 2018 Pan Pacific Lymphoma Conference, Ansell, chair of the Lymphoma Group at Mayo Clinic, discussed overcoming immune evasion in lymphoma.
OncLive: What is the issue with immune evasion in Hodgkin lymphoma?
One of the big challenges in lymphoma is that many immune cells are present right in the tumor, but somehow those immune cells are not killing the tumor cells. The key question is, how does the tumor hide from the immune system as efficiently as it does? Actually, there are many barriers to a good immune response in lymphoma. The cells that are there are pretty exhausted from being persistently activated, and sometimes there are other cells in the neighborhood that are suppressing their activity.
Also, there are many proteins that are being made on the tumor cell like cytokines, which activate the immune system but then exhaust it over time. With all that going on, plus the immune-suppressive macrophages present in the tumor, the real challenge is working out how to get the T cell to kill the tumor cell efficiently. There are a lot of strategies being tried to test that now.
What are some of the strategies?
One of the real successful strategies has been to prevent T-cell exhaustion. T cells basically get activated, make proteins such as PD-1 as a receptor on the cell surface, and that then puts them at risk for being suppressed by PD-L1 or PD-L2. Other receptors, such as TIM-3 and LAG-3, are important and those begin to increase as the cell becomes more exhausted. A strategy to keep the immune system engaged is to block these negative signals. Blocking PD-1 has been very successful in lymphoma, but now new trials blocking TIM-3 and LAG-3 are all in progress.
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