The immune system has recently been implicated as an accessory to cancer formation. Although it was previously known that immune cells are present within a tumor, they were thought to be there to fight the tumor cells. We now know that the tumor cells can 'trick' the immune cells into submission and in some cases even have the immune cells working to help the tumor survive in a process called immune evasion.
Tumors are often infiltrated by cytotoxic T cells. As a normal cell became a tumor cell, the antigens on its surface change to neoantigens. The T cells should recognize the neoantigens as non-self and attack the cancer cell. But tumor cells can use a protein called programmed death ligand 1 (PD-L1) to prevent T cell activation. By over-expressing this protein on the tumor cell surface, the tumor cell prevents being killed by cytotoxic T cells. Tumor cells over-expressing PD-L1 have been shown to respond to immune-oncology (I-O) therapy that targets the interaction of this protein with its receptor. Over-expression of PD-L1 is detected with an immunohistochemical (IHC) stain.
Regulatory T cells (Tregs) and antigen presenting cells (APC) can actually help the tumor cell grow by inhibiting the immune response. Tregs downregulate the activation of T cells in part through a protein called lymphocyte-activation gene 3 (LAG-3). LAG-3 leads to T-cell exhaustions and decreased cytotoxic T cell function. Levels of LAG-3 expression can also be measured by IHC. APCs such as myeloid-derived suppressor cells (MDSCs) can also cause T-cell exhaustion. In this case the cytotoxic T-cells may be present in the tumor; however they are not killing the cancer cells. I-O therapy is working to reactivate the cytotoxic T-cells to ensure they recognize the tumor cells as foreign and attack them appropriately.
Nearly every biological process in the cell has an on and an off switch to keep a healthy check and balance system. Tumor cells are masters at usurping these processes and using them to promote tumor cell escape and invasion. Researchers are working to develop targeted therapies that allow normal cells to regain control of these systems.
