The role of PD-1/PD-L1 and application of immune-checkpoint inhibitors in human cancers

Abstract

Programmed cell death protein-1 (PD-1) is a checkpoint receptor expressed on the surface of various immune cells. PD-L1, the natural receptor for PD-1, is mainly expressed in tumor cells. Studies have indicated that PD-1 and PD-L1 are closely associated with the progression of human cancers and are promising biomarkers for cancer therapy. Moreover, the interaction of PD-1 and PD-L1 is one of the important mechanism by which human tumors generate immune escape. This article provides a review on the role of PD-L1/PD-1, mechanisms of immune response and resistance, as well as immune-related adverse events in the treatment of anti-PD-1/PD-L1 immunotherapy in human cancers. Moreover, we summarized a large number of clinical trials to successfully reveal that PD-1/PD-L1 Immune-checkpoint inhibitors have manifested promising therapeutic effects, which have been evaluated from different perspectives, including overall survival, objective effective rate and medium progression-free survival. Finally, we pointed out the current problems faced by PD-1/PD-L1 Immune-checkpoint inhibitors and its future prospects. Although PD-1/PD-L1 immune checkpoint inhibitors have been widely used in the treatment of human cancers, tough challenges still remain. Combination therapy and predictive models based on integrated biomarker determination theory may be the future directions for the application of PD-1/PD-L1 Immune-checkpoint inhibitors in treating human cancers.

Smoking Cessation after Cancer Diagnosis and Enhanced Therapy Response: Mechanisms and Significance

“…Several smoking-related cancers, such as head and neck cancer, bladder cancer, etc., also respond to immunotherapy [ 9 , 10 , 11 ]. Not surprisingly, checkpoint inhibitors such as Pembrolizumab (Keytruda), Nivolumab (Opdivo), Ipilimumab (Yervoy), Duryalumab (Imfinzi), Cemiplimab (Libtayo), and Atezolizumab (Tecentriq) are widely used as first-line therapy against non-small-cell lung cancer (NSCLC) based on the programmed death-ligand 1 (PD-L1) status of the tumors [ 12 , 13 ]. Checkpoint inhibitors are known to be significantly more effective in tumors with higher mutational burden, including lung cancers and skin cancers such as melanoma [ 14 , 15 ].…”

Long-term benefit of immunotherapy in a patient with squamous lung cancer exhibiting mismatch repair deficient/high microsatellite instability/high tumor mutational burden: A case report and literature review

“…However, it remains challenging to find patients exhibiting long-term responses to immunotherapy in the present era of precision medicine. The predictive biomarkers of immune checkpoint inhibitor efficacy include the tumor cell surface PD-L1 expression level, tumor mutational burden (TMB), mismatch repair deficiency/high microsatellite instability (dMMR/MSI-H), and tumor-infiltrating lymphocytes (2)(3)(4).…”

PD-1 Checkpoint Blockade in Patients for Acute Myeloid Leukemia after HSCT Relapse Resulted in Severe GVHD and sHLH

“…General management includes immunosuppressant withdrawal, chemotherapy, donor lymphocyte infusion ( DLI ), chimeric antigen receptor (CAR) T-cell therapy, and second transplantation, which are not very effective. At present, ICI is increasingly applied to solid tumors such as lymphoma, lung cancer, and melanoma, and has achieved encouraging therapeutic effects [ 4 ]. Therefore, increasing attention has been paid to the treatment of ICI .…”