Preventing cancer from returning in the body is an integral part of any anti-cancer treatment plan. New discoveries from a research group out of the University of Pittsburgh highlight an important protein involved in releasing the immune system to use all of its power to prevent recurring bouts of cancer.
"Our findings point to an important new biological anti-tumor mechanism that we can exploit to provide durable, long-term immune response against tumors,” explained Dario A.A. Vignali, PhD.
The mechanism he mentions is the relationship between the newly studied Neuropilin-1 (NRP1) protein and effector T cells responsible for targeting and destroying cancerous cells in the body. At the beginning of this study, researchers hypothesized that NRP1 might be a vital component of immune suppression in response to cancer.
Why would the body suppress the immune response to cancer at all? The immune system has regulatory mechanisms in place to prevent the immune system from overreacting to stimuli, but in the case of cancer, researchers want to give the immune system all the power it can get. This is the foundational idea behind immunotherapy.
Immunotherapy that targets cancer works by blocking checkpoint inhibitor proteins, giving effector T cells an all-access pass to targeting cancer cells. The problem? Two-thirds of patients don’t respond to this type of treatment. There needs to be a way to increase the number of people who can be helped by immunotherapy, and NRP1 may be the key.
Going into the study, researchers were familiar with NRP1 on surface of non-effector T cells, but the activity of NRP1 related to effector T cells was unclear. They used a mouse model - genetically modified to lack NRP1 from the surface of effector T cells – to see what would happen after grafting tumor cells to the mouse model.
While they expected the tumors to grow little to not at all compared to control mice with fully functional NRP1, instead they saw zero difference in tumor growth between experimental and control. However, when researchers mimicked cancer recurrence by removing the original tumor cells and grafting them elsewhere, NRP1-deficient mice showed significantly less tumor growth compared to control mice.
This stark difference showed the researchers that NRP1 is fundamental for T cell development and immune memory. T cells with NRP1 intact on their cell surface became “exhausted and ineffective in fighting cancer,” especially when the battle continued for a long time.
Removing NRP1 from the cell surface boosted immune memory, explaining why when the same tumor cells were grafted for a second time but in a different location in the mouse models lacking NRP1 on effector T cells, the mice were exceptionally successful at suppressing further growth.
Interestingly, these findings correspond with studies of human T cells extracted from the blood in cases of skin cancer or cancer in the head or neck. Advanced cancer patients exhibited higher levels of NRP1 on so-called “memory” effector T cells compared to early-stage cancer patients.
Drugs targeted NRP1 are currently being tested in combination with anti-PD1 immunotherapies.