In order to effectively clear out tumor cells, the immune system needs to be able to generate an appropriate inflammatory response. However, the fact that most of our immune cells contain a fail-safe mechanism to ensure they are not constantly activated is a double-edged sword. There are a number of markers found on both tumor cells and antigen presenting cells that can downregulate or suppress T cells once the corresponding ligand is bound.
Researchers are now looking into how they can prevent T Cells from binding these tolerance-inducing ligands. This would keep the T Cells active and ready to battle cancer. These markers have come to be known as “immune checkpoint receptors”. Although a number of immune checkpoints are being looked at, the most well-studied combinations include PD-1/PD-L1, CTLA-4/CD80 and CD86, LAG-3/MHC II, Tim-3/Galectin 9, and TIGIT/CD155 (PVR). Additionally, the use of recombinant cytokines, such as IFN-α and IL-2, augment anti-tumor inflammatory responses, and have been used in the clinic as a part of immunotherapeutic regimens to treat various malignancies. The direct injection of molecules involved in inflammation, such as TLR9 and anti-OX40 antibodies, has also shown to be effective in providing long-term anti-tumor protection by promoting and maintaining activation of the immune system.
Click on the receptor/ligand or cytokine names below in order to learn more about their cell distribution, function, and therapeutic role in treating cancer. You can also take a look at our thorough Cancer Immunoediting poster, which can be requested for free from our literature page.