In recent years, anti-PD-1 and PD-L1 antibodies have been postulated as the great promise in the field of cancer immunotherapy . There are more and more clinical trials with monoclonal antibodies against these targets that are being carried out, with results that, far from being the definitive therapy, are encouraging to advance in the treatment of this disease.
In this entry we summarize the function of the immunomodulatory molecules PD-1 and PD-L1, as well as the current state of progress in immunotherapy .
Route Pd-1 / Pd-L1
The PD-1 receptor and its PD-L1 / PD-L2 ligands belong to the family of immune control proteins, and act as co-inhibitory factors to modulate the response of T cells and prevent chronic autoimmune inflammation.
When T lymphocyte receptors recognize surface antigens that identify a cell as cancer, they are activated to kill it. But when a T cell is activated, a stop signal is also required to ensure that over-activation will not occur. One of the ways that this activation of T lymphocytes is regulated is through inhibition receptors such as PD-1 (programmed death receptor, also known as CD279), present on the surface of T cells.
Upon activation, T lymphocytes increase PD-1 receptor expression that will allow them to receive the deactivated signal. This signal will be produced after the binding of this receptor to its PD-L1 or PD-L2 ligand, which are normally expressed on the surface of dendritic cells and macrophages, and which will cause the reduction of cytokine production and suppression of proliferation. of T cells.
And it is precisely this mechanism that a multitude of tumors have integrated in order to block their recognition through the expression on their surface of the PD-L1 and PD-L2 proteins, thus escaping the action of the immune system and continuing proliferating. The PD-1 / PD-L1 pathway therefore represents an adaptive immune resistance mechanism that tumor cells develop in response to endogenous anti-tumor activity.
Immunotherapy With Anti Pd-1 And Pd-L1 Antibodies
The cancer immunotherapy aims to overcome the ability of tumor cells to resist the endogenous immune response, by stimulating the immune system itself of each patient.
In the case at hand, a molecule capable of blocking the PD-1 receptor present on the surface of lymphocytes, or the PD-L1 and PD-L2 ligands expressed by cancer cells, would prevent the binding of both and therefore Therefore, there would be no immunomodulatory signal, allowing the T cells to continue active against the tumor.
Have developed monoclonal antibodies against PD-1 (Pembrolizumab, Nivolumab) and PD-L1 (Atezolizumab), known inhibitors of points immunological control capable of blocking the binding and stimulate immune response against tumor cells. Proof of this are the numerous clinical trials with anti-PD-1 and PD-L1 antibodies that are being carried out, with promising results especially in non-small cell lung cancer, melanoma, renal carcinoma and bladder cancer.