The Programmed cell death ligand-1 (PD-L1), an immune checkpoint molecule, is the ligand of Programmed cell death protein 1 (PD-1). They are crucial molecules in maintaining immune homeostasis. PD-L1/PD-1 axis regulates the initiation and maintenance of tolerance and protects tissues from autoimmune responses,however, cancer cells can use the PD-1/PD-1 axis to evade the anti-tumor response of immune cells. Increased PD-L1 expression is directly associated with poor prognosis in hepatocellular carcinoma (HCC). Although immunotherapy with immune checkpoint inhibitors (ICIs) are leading therapy in cancer treatment, using biomarkers to regulate immune checkpoints at the RNA level is considered a promising tool in novel therapeutic approaches. Increasing evidence has reported that miRNAs are critical regulators of tumor development. Hence, we performed a current systematic review to explore PD-L1 inhibiting miRNAs involved in hepatocellular carcinoma. Five databases were systemically searched to obtain the relevant original articles. Consequently, seventeen studies were included in the current systematic review. According to obtained literatures, some microRNAs, namely miR-194-5p,-675-5p, 194-5p,-1,-455-5p,-223-3p,-513,-195,-506,-329-3p,-424,-411-5p,-182-5p,-200,-378a-3p,-570,-200c, and-513a-5p can inhibit PD-L1 expression in HCC cells. These can ultimately reduce tumor proliferation, inhibit tumor migration, stimulate the chemosensitivity of cancer cells, and induce apoptosis in tumor cells. Moreover, the investigated miRNAs were further analyzed using miRNA target prediction online tools to highlight the future direction of their functions in HCC. HIGHLIGHTS Cancer cells can use the PD-1/PD-1 axis to evade the anti-tumor response of immune cells. Increased PD-L1 expression is directly associated with poor prognosis in hepatocellular carcinoma. Several microRNAscan inhibit PD-L1 expression in HCC cells.

Introduction. The genetic variations of co-stimulatory molecules can affect the extent of T cell activity during T-cell mediated immunity, especially in transplant patients. This study aimed to investigate the association of Programmed cell death 1 (PDCD1) and Programmed cell death 1 ligand 1 (PDCD1LG1) gene polymorphisms with clinical outcome of kidney transplantation. Materials and Methods. A total of 122 patients with a kidney transplant were included in this retrospective study. Patients were classified into two groups of biopsy-proven acute allograft rejection (AAR) and stable graft function (SGF) during the 5-year followup period. Four single nucleotide polymorphisms in PDCD1 and PDCD1LG1 were determined in the groups of patients as well as in 208 healthy control individuals. Results. The frequencies of PD-1. 3 (+7146 G > A), PD-1. 9 (+7625 C > T), PD-L1 (8923 A > C), and PD-L1 (+6777 C > G) genotypes and alleles were not significantly different between the AAR and SGF groups. In comparison with healthy controls, PD-1. 9 (+7625 C > T) genotype and T allele were significantly more frequent in all of the patients and in those with SGF. Overall, 27 of 122 kidney allograft recipients experienced delayed graft function, and a higher frequency of PD-1. 9 (+7625 C > T) genotype and T allele was observed in this group versus those without delayed graft function. Similarly, a significant high frequency of this genotype was found among the AAR subgroup of patients with delayed graft function. Conclusions. Our results indicate that potentially functional genetic variation in PDCD1 can influence the outcome of kidney transplantation.

Apoptosis or Programmed cell death is known as a conserved gene-directed mechanism for the specific elimination of unnecessary or unwanted cells from an organism and is involved in many immune system mechanisms and diseases. The main differences of this pathway with cell necrosis as two main pathways for elimination of unwanted cells are the absence of inflammation and the restricted effect on target cells. Apoptosis has an important role in biological processes such as normal development, tissue homeostasis, elimination of destroyed cells or virus infected cells and remove of self antigen-activated immune cells. Apoptosis is important for regulation of cell growth and proliferation, development and body health and many autoimmune diseases, cancers and viral infections are the result of impaired or inhibited Programmed cell death. Therefore the main objective of apoptosis research is to identify molecular components and regulatory mechanisms specially Bcl-2 and IAP family as the most important regulators of apoptosis and this information may lead to application of therapeutic agents that can modulate this process in the treatment of neurodegenerative disorders and proliferative diseases such as cancer.

Dear Editor, We read with interest the article published in the Iranian Journal of Kidney Diseases, entitled “ Association of Programmed cell death 1 and Programmed cell death 1 ligand Gene Polymorphisms With Delayed Graft Function and Acute Rejection in Kidney Allograft Recipients...

Programmed cell death-1 (PD-1) and its ligands, PD-L1 and PD-L2, have been regarded as important immune system regulatory molecules. The aberrant expression of the molecules has been related to several autoimmune disorders. This study is aimed to assess the mRNA expression level of PD-1, PD-L1, and PD-L2 molecules in the peripheral blood mononuclear mells (PBMCs) from multiple sclerosis (MS) patients. PBMCs were isolated from the whole blood of 50 MS and 50 healthy individuals. Total RNA content of the leukocytes was extracted. Then, cDNA was synthesized from the extracted RNA. Afterwards, quantitative analysis of PD-1, PD-L1 and PD-L2 was carried out through Real Time PCR using the TaqMan gene expression assays. Relative expression of PD-1 and PD-L1 in PBMCs from MS patients was significantly lower compared with the healthy control group (p=0. 003 and 0. 012, respectively). However, no significant difference was observed in the expression level of PD-L2 between patients and healthy individuals. Relative expression of PD-1 correlated with expanded disability status scale score (EDSS) of the patients (r=-0. 763, p=0. 008). Downregulation of the immunosuppressive molecules, PD-1 and PD-L1, may imply that over-activation of immune cells in multiple sclerosis occurs through signaling dysfunction of these molecules and PD-L2 plays no important role in this context.