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Immun-Checkpoint - Info

Immun-Checkpoints

A central component of our immune system are T lymphocytes (short: T cells). They belong to the group of leukocytes (white blood cells). In addition to B lymphocytes, they are the most important part of the adaptive immune response. There are receptors on the surface (membrane) of T lymphocytes called immune checkpoints. Because of their influence on the immune response, they are subdividable into anti-inflammatory and proinflammatory immune checkpoints.

The corresponding counterparts to the receptors, the ligands, are located on the surface of other cells. Tumor cells show an overexpression of these proteins, allowing them to escape recognition by T cells. This phenomenon is also called immune evasion.

In medicine, the field of cancer immunotherapy (immune checkpoint therapy) is concerned with immune checkpoint inhibitors. These are substances that bind to immune checkpoints. Thereby, they prevent the possibility of the tumor cell to escape the recognition by T lymphocytes. Consequently, the body's immune response in the fight against the tumor cell is supported by immune checkpoint inhibitors.

 

Fig.1.: Up. The binding of the over-expressed ligand PD-L1 on the surface of the tumor cell to the immune checkpoint PD-1 inhibits the attack of the T cell.
Down. Blocking this interaction by means of an anti-PD-1 or an anti-PD-L1 antibody prevents the immune evasion of the tumor cell and allows the attack of the T cell on the tumor cell.

 

The best-known immune checkpoints include PD-1 and CTLA-4. James P. Allison and Tasuku Honjo received the Nobel Prize for Medicine in 2018 for their research on immune checkpoints. The two immuno-checkpoint inhibitors Nivolumab and Ipilimumab were developed against them.

The anti-VISTA represents the revolution in cancer research on immune checkpoints. This monoclonal antibody (13F3) binds to murine V-domain immunoglobulin suppressor of cell activation (VISTA), also known as PD-1H and B7-H5. VISTA is a negative immune checkpoint that inhibits T cell cytokine production and proliferation. Tumor infiltrating lymphocytes (myeloid cells and regulatory T cells) show a marked overexpression of VISTA on their surface. The blocking of VISTA by means of the monoclonal 13F3 antibody has led to delayed tumor growth and represents a promising approach for future cancer immunotherapy.

References regarding the clone 13F3: