The PD-1/PD-L1 pathway is normally involved in promoting tolerance and preventing tissue damage in the setting of chronic inflammation. Programmed death 1 (PD-1) and its ligands, PD-L1 and PD-L2, deliver inhibitory signals that regulate the balance between T cell activation, tolerance, and immunopathology. The PD-1 programmed death-ligand 1 (PD-L1) is a transmembrane protein that binds to the programmed death-1 receptor (PD-1) during immune system modulation. This PD-1/PD-L1 interaction protects normal cells from immune recognition by inhibiting the action of T-cells thereby preventing immune-mediated tissue damage.
Inactivation of T-cells limits damage to normal tissues.
Dysregulation in cancer
Harnessing the immune system in the fight against cancer has become a major topic of interest. Immunotherapy for the treatment of cancer is a rapidly evolving field from therapies that globally and non-specifically stimulate the immune system to more targeted approaches. The PD-1/PD-L1 pathway has emerged as a powerful target for immunotherapy. A range of cancer types have been shown to express PD-L1 which binds to PD-1 expressed by immune cells resulting in immunosupressive effects that allows these cancers to evade tumour destruction. The PD-1/PD-L1 interaction inhibits T-cell activation and augments the proliferation of T-regulatory cells (T-regs) which further suppresses the effector immune response against the tumour. This mimicks the approach used by normal cells to avoid immune recognition. Targeting PD-1/PD-L1 has therefore emerged as a new and powerful approach for immunotherapy directed therapies.
Upon binding to PD-1, PD-L1 delivers a suppressive signal to T cells and an antiapoptotic signal to tumor cells, leading to T cell dysfunction and tumor survival.
Anti PD-1/PD-L1 Immunotherapy
Targeting the PD-1/PD-L1 pathway with therapeutic antibodies directed at PD-1 and PD-L1 has emerged as a powerful therapy in those cancer types displaying features of immune evasion. Disrupting the PD-1/PD-L1 pathway with therapeutic antibodies directed against either PD-1 or PD-L1 (anti-PD-L1 or anti-PD-1 agents) results in restoration of effector immune responses with preferential activation of T-cells directed against the tumour.
A range of cancer types including:
- renal cell carcinoma
- lung cancers
- cancers of the head and neck
- gastointestinal tract malignancies
- ovarian cancer
- haematological malignancies
are known to express PD-L1 resulting in immune evasion.
Anti-PD-L1 and anti-PD-1 therapy has been shown to induce a strong clinical response in many of these tumour types, for example 20-40% in melanoma and 33-50% in advanced non small cell lung cancer (NSCLC). A number of these antibodies, for example anti-PD-1 directed agents Nivolumab and Pembrolizumab, have now received FDA-approval for the treatment of metastatic NSCLC and advanced melanoma.
Blocking the PD-1/PD-L1 interaction enables T cell activation resulting in increased tumour cell death and elimination.
Immunofocus PD-L1 IHC DETECTION ASSAY
Oncologica’s laboratory-developed test for assessing PD-L1 expression in tumours is based on the immunohistochemical staining of routine diagnostic histological material with an anti-PD-L1 antibody, clone E1L3N, Cell Signaling Technology. Semi-quantative analysis is performed to derive a Tumour Proportion Score for PD-L1 expression which can be used as a guide to predict response to anti-PD-1 and anti-PD-L1 directed therapies.
- Companion diagnostic for immunotherapy
- Predictive of response to anti PD-1/PD-L1 therapies
- Applicable to a broad range of tumour types
- Performed on routine histological samples
- Analysis performed by qualified pathologists
- 3 Working days turnaround time