Immunohistochemical Assessment of Programmed Death Ligand 1 PDL-1 and Autophagy Marker LC3B in Glioblastoma

Gliomas account for almost 30% of all primary brain tumours, and are responsible for the majority of deaths from primary brain tumours .

Glioblastoma is the most common primary malignant brain tumor in adults, accounting for 60-70% of gliomas and 15% of primary brain tumors . Glioblastoma is the most aggressive and undifferentiated type of glioma and designated WHO Grade IV .

Programmed cell death 1 (PD-1) is a protein receptor that functions as an immune checkpoint. It conveys an inhibitory signal to T cells. In cancer, It protects tumors from cytotoxic T lymphocytes(CTL) . The inter¬action of PD1 with its ligand PD-L1 on surface of T-cells suppresses their function and hindering the recognition of tumor cells .PD-L1 expression is inversely correlated with the density of intratumoral CD8+(Cluster of Differentiation 8) T cells .

Autophagy is a catabolic process that leads to cellular degradation and recycling by lysosomal digestion. Thus allowing cells to adapt to stress). Autophagy promotes tumor development, progression and therapy resistance due to its pro-survival role under stress as radiation and chemotherapy. LC3B(microtubule associated protein light chain 3 B) is a commonly used marker to monitor autophagy .PD-L1 has been related to autophagy. Recent findings from experiments with murine melanoma cells and human ovarian cancer cells indicated cells expressing high levels of PD-L1 are more sensitive to autophagy inhibitors than cells that weakly express PD-L1. This finding provides potential opportunities for using autophagy inhibitors in PD-L1-overexpressing cells as a new avenue in cancer management . Thus not studied in GBM before ,our study is pure novel study.

The authors hypothesize that both PD-L1 and LC3B are highly expressed in GBM cells and high PDL1 expression is associated with low CTL count . It is possible that elevated levels of PD-L1 and LC3B markers indicate immune inhibition ,increased autophagy and poor prognosis thus their inhibition will have therapeutic benefit.