Prospect of liquid biopsy application for precise medication of PD-1/PD-L1 inhibitor

In recent years, liquid biopsy has been widely used in cancer early screening, companion diagnosis, drug efficacy prediction and monitoring, etc. Liquid biopsy has the advantages of real time, noninvasive, sequential sampling etc., and is one of the most promising cancer diagnosis methods. Liquid biopsy includes circulating tumor cells (CTC), cell-free circulating tumor DNA (ctDNA), and exosomes to obtain tumor lesion information. For early screening and diagnosis of tumors, targeted drug prediction, dynamic monitoring of efficacy, drug resistance analysis and prognosis evaluation, it is a representative diagnostic technology in the contemporary “precise medical” system. At the same time, the revolutionary immunotherapy puts forward higher requirements for the precise diagnosis, especially for the precise medication of programmed death 1/programmed death ligand 1(PD-1/PD-L1) inhibitors. In normal organisms, PD-L1 (programmed cell death-Ligand 1) is a protein expressed on the cell surface, also known as B7-H1 protein. It binds to PD-1 protein (programmed death receptor-1) on effector T cells, conducts immunosuppressive signals, and inhibits the activity of immune effector T cells. The expression of PD-L1 on the surface of tumor cells is the material basis for tumor escape from immune cell attack and a marker for poor prognosis. PD-1/PD-L1 immunotherapy is being used for other larger tumors. Currently, hundreds of clinical trials of monotherapy and combination therapy are being carried out intensively, to exploit the clinical potential and value of a largest number of such IO drugs. PD-L1 companion diagnostics is a screening for responders to drugs by identifying the expression of the drug target PD-L1 protein. The Merck East team identified patients with non-small cell lung cancer who responded to drugs by using tissue-expressed PD-L1>50% criteria, segmented patient populations, and identified potentially beneficial patients. This precise medical strategy was obtained in clinical trials and commercial promotion. Tumor mutation burden (TMB) is the number of somatic mutations in the whole genome after accounting for germline DNA variants. Studies have found that if there are many genes mutated in tumor tissues, the possibility of activating the body’s immune system is high, and the probability of benefiting from immunotherapy is greater. Therefore, TMB high mutations are also an important biomarker for predicting the effectiveness of PD-1 antibodies. Many existing immunotherapies inhibit the PD-1/PD-L1 pathway, and if immune T cells can be blinded by cancer cells, they can remain active and attack cancer cells. Researchers expect to be able to find “indications” in the patient’s blood through a simple blood test to tell the doctor if the immunotherapy is effective. How to improve the efficacy of PD-1/PD-L1 inhibitors, accurate prediction and dynamic monitoring of therapeutic effects has become the most concerned issue in the clinical community. In this paper, we compare several liquid biopsy technologies including CTC, ctDNA and exosomes for the prediction and surveillance of PD-1/PD-L1 inhibitor drugs in immunotherapy.