Cancer and Immune Checkpoint

Cancer and Immune Checkpoint In tumor, cells will get many new characters from common cells to cancer cells.

Compare with common cells, the feature of genetics and epigenetics has changed in cancer cells. The immune system can recognize cancerous cells and induce the immune response of anti-tumor. Therefore, the balance can be kept when a few cells are canceration. But immune suppression related with tumor blocks the effective immune response. T cells play a critical role in the process of effective immune response of anti-tumor. Due to the importance of T cells in the immune response, when T cells are activated by antigen recognition signals, various co-activation signals and co-suppression signals are used to finely adjust the intensity and quality of T cell responses.

These inhibition signals are immune checkpoint. The significance of immune checkpoint is to participate in maintaining immune tolerance to autoantigens, avoiding autoimmune diseases, and avoiding damage to tissues caused by excessive activation of immune responses. In cancerous tissues, tumor cells can use immune checkpoints to inhibit T cell activation and thus evade immune killing. This is a key point in tumorigenesis in vivo. Therefore, enhancing the activation of T cells through different strategies is of great significance for tumor immunotherapy. The blocking of immune checkpoints is one of the effective strategies for enhancing T cell activation.

The most in-depth studies about immune checkpoints currently include cytotoxic T lymphocyte antigen 4(CTLA-4), programmed death protein 1 and its ligands(PD-1/PDL-1), and its targeted inhibitors have entered clinical trials, and the US Food and Drug Safety Commission have also approved the first-generation immune checkpoint inhibitor ipilizumab (a monoclonal antibody that blocks CTLA-4).

It is used to induce a sustained anti-tumor response to treat melanoma. At the same time, drugs that inhibit the checkpoint PD1 and its ligand PDL-1 have shown good therapeutic effects in many tumor treatments. In addition to the classic checkpoints CTLA-4 and PD-1/PDL-1, many new checkpoints have been discovered in recent years as potential immune targets, such as 4-1BB, OX40, CD27, LAG3, CD224, TN-FRSF25.

Etc., drugs against these checkpoints block the transmission of inhibitory signals and induce antitumor effects of T cells.