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
The Oncologica Immunofocus PD-L1 immunocytochemistry assay qualitatively identifies Programmed Cell Death Ligand 1(PD-L1) protein in sections of formalin fixed, paraffin embedded cancer tissues. The Laboratory Developed Test utilises the RUO rabbit monoclonal antibody clone E1L3N (Cell Signalling Technologies) and Leica Bond III instrumentation. The assay has been internally verified by Oncologica to reflect clinical use and falls within the scope of UKAS/ISO 15189:2012 accreditation.
- 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