In recent years, immune checkpoint inhibitors (anti-PD-1, anti-PD-L1, and anti-CTLA-4 antibodies) have exhibited potential therapeutic effects for advanced HCC.
Concomitant with patient-derived M-MDSC suppression by i-BET762, combined treatment with anti-PD-L1 synergistically enhanced TILs, resulting in tumour eradication and prolonged survival in the fibrotic-HCC mouse model.
Finally, using SP263, the mean number of PD-L1-positive cells was 11.3 ± 12.6 in HCC from deceased patients, versus 4.7 ± 5.2 in alive patients (p = 0.039).
The clinical therapy that dilapidates PD1 or PD-L1-mediated cancer tolerance has pushed out the need to uncover the molecular regulation of PD-L1 overexpression in the tumor cell.
The combination of PD-1/PD-L1 blockade and macrophage-targeted therapy will exert synergetic anti-tumor effect and shape the future of cancer immunology and immunotherapy.
Programmed death ligand-1 (PD-L1) in conjunction with tumor-infiltrating lymphocytes (TILs) has been studied as a potential mechanism of "immune escape" in several human malignancies.
Among these checkpoints are tytotoxic T-lymphocyte-associated antigen 4, checkpoints programmed death-1 and programmed death-ligand 1; their blockades have been approved by the Food and Drug Administration for therapy of melanoma and other types of cancers.
Our study suggests that blocking PD1/PDL1 pathway may become an effective mode of treatment in cancer immunotherapy especially for Renal Cell Carcinomas.
Mut-p53-induced epithelial-mesenchymal transition (EMT) plays a crucial role in the invasion and metastasis of endocrine carcinomas, and Mut-p53 is involved in cancer immune evasion by upregulating PD-L1 expression.
The success of T cell-directed checkpoint inhibitors of CTLA-4 and PD-1/PD-L1 has opened a new approach for cancer immunotherapy and resulted in extensive research on immune checkpoints.
Anti-programmed cell death 1 (PD-1) and anti-programmed cell death ligand 1 (PD-L1) antibodies are novel immunotherapies for cancer that can induce immune-related adverse events (irAEs).
Currently, the strategy of PD-1/ PD-L1 blockade has already been applied to clinical cancer therapy, providing evidences that PD-1 signal is one of the main factors of cancer immune escape in humans.
Although both anti-PD-1 antibody and treatments using anti-PD-L1 antibody are currently in clinical use, their therapeutic effects vary according to cancer type.
Expert opinion: Data supporting the patent demonstrate the ability of LAG-3Ig and PD-1/PD-L1 to be useful in T cells activation, in addition to the reports showing that LAG-3 and anti-PD-1 and PD-L1 antibodies are therapeutic agents against cancer.
Importantly, changes in immunosuppressive MDSCs frequency and PD-L1 expression levels may serve as biomarkers of hypoxia levels in cancer affected tissues that can benefit from hyperoxia treatments.
Targeting PD-1/PD-L1 to treat cancer has shown benefits in many patients, suggesting a promising opportunity to target this pathway in autoimmune and inflammatory disorders.
Although many antibodies targeting PD-1/PD-L1 have been developed to block their interaction for the treatment of cancer, the reduced response rate and resistance to the therapies call for further comprehension of this pathway in the tumor microenvironment.