Our body continuously mounts an immune response against newly formed cancer cells. Cells of the immune system (like T lymphocytes) can recognise specific proteins projecting from cancer cells and mark them for destruction. But cancer cells are normal cells that turned rogue. So, in some cases, both normal cells and cancer cells have the same proteins projected. As a result, the body’s immune system could inadvertently mark normal cells for destruction. To prevent this, the immune system has evolved a negative regulation mechanism. In this mechanism, immune cells are inhibited from interacting with some of the projecting proteins that are found in normal cells. Since cancer cells could also have these proteins, they escape from the immune system and continue to grow.
The negative regulation mechanism I just described above is necessary to prevent normal cell death but it also reduces the chances for the immune system to mark cancer cells for destruction. Scientists have been working on developing strategies to modulate the immune response so that cancer cells can be more effectively targeted by the body’s immune system.
Anti-cancer immune response regulation by Rasal1
Researchers have now discovered a new cell therapy approach that boosts the immune response of T lymphocytes to malignant tumours (1). This is based on the protein Rasal1 which was found to be negatively regulating T-cell cancer immunity. Rasal1 interacts with a key receptor protein that detects and responds to cancer proteins.
In their paper, published in Nature Communications, they describe a mechanism by which Rasal1 inhibits the T-cells response. They also observed that removing Rasal1 protein in mice reduces tumour growth. They argue that when Rasal1 was removed, T-cells were more proactive against induced tumours thereby reducing overall tumour growth (1).
Overall, our findings identify a novel TCR-associated protein that negatively regulates T-cell activation and antitumor immunity.Thaker et al., 2019
The authors believe that this mechanism can be exploited in cancer therapy. Development of specific inhibitors against Rasal1 or similar negative regulators of anti-tumour response of the immune cells seems to be feasible. However, like many have pointed out and as I have written here, increasing the anti-tumour response may also hyper-activate immune cells against normal cells which will have side-effects like any other currently existing cancer therapies. How can we (and the immune cells of our body) distinguish between normal and cancer cells?
- 1.Y. R. Thaker, M. Raab, K. Strebhardt, C. E. Rudd, GTPase-activating protein Rasal1 associates with ZAP-70 of the TCR and negatively regulates T-cell tumor immunity. Nat Commun (2019), doi:10.1038/s41467-019-12544-4.