PD-L1 is a transmembrane protein expressed in cancer cells that down-regulates immune responses through binding to its two inhibitory receptors, PD-1 and B7.1. PD-1 and B7.1 are inhibitory receptors expressed on T cells following T-cell activation, sustained expression of these receptors are seen in states of chronic stimulation such as in chronic infection or cancer.
Ligation of PD-L1 present on the cancer cells with PD-1 on the T-cells inhibit their proliferation, leading to inactivation of T-cells.
Increase in the expression of PD-L1 on tumor cells has been reported to decrease the anti-tumor immunity, resulting in immune evasion. Therefore, interruption of the PD-L1/PD-1 pathway represents an attractive therapeutic strategy in treatment of Non-small cell lung cancer (NSCLC) and other tumors.
For patients with Metastatic (Stage IV NSCLC), NCCN developed an algorithm for initial therapy. Patients with EGFR, ALK, or ROS1 mutations or rearrangements at diagnosis, which collectively constitute about 25% of NSCLC, should receive targeted therapy as first-line treatment (category 1 recommendation). For patients with NSCLC whose tumors are positive for PD-L1 while being negative or unknown for other mutations or rearrangements in EGFR, ALK and ROS1 the drug Pembrolizumab is recommended as a first-line choice.
PD-L1 Testing in our laboratory is done by Ventana PD-L1 (SP263) Assay. This assay is CE (European Conformity) Labelled to inform treatment decisions in Lung Cancer Patients being considered for Pembrolizumab immunotherapy as a first line of treatment.
Recommended positive cut off for PDL-1 (Clone SP263) in Lung cancer (NSCLC) is : >1= 50% of tumor cells. Studies showed superior progression free survival and overall survival in first-line treatment of metastatic NSCLC with PDL-1 expression >/= 50%.
Test Name:- IMMUNOHISTOCHEMISTRY, PD-L1
Specimen:- Submit tumour tissue in 10% formal-saline OR formalin fixed paraffin embedded block.
Ship at room temperature. Provide a copy of the histopathology report. Indicate site of biopsy and provide clinical history.
TAT: Sample Daily by 6 pm; Report : Blocks: 5 Days ; Tissues : 7 Days