Inflamed Tumour Markers

Tumour-infiltrating immune cells are observed in chronic inflamed tumours and their microenvironments.

PD-L1

Programmed death ligand 1 (PD-L1) is a protein ligand that binds to programmed death receptor-1 (PD-1). PD-1 is an immune checkpoint receptor. PD-L1 is expressed by lymphoid, endothelial, and epithelial cells. Expression of PD-L1 on tumour cells helps in evading immune response by inhibiting the activity of cytotoxic T cells.

Importance

  • PD-L1 is a protein ligand for the immune checkpoint receptor PD-1.
  • PD-L1 is expressed by lymphoid, endothelial, epithelial cells, and tumour cells, while PD-1 is expressed on the surface of cytotoxic T cells.
  • Expression of PD-L1 by tumour cells helps to inhibit the activity of cytotoxic T cells, thus evading immune response.

PD-L2

Programmed death ligand 2 (PD-L2) is a protein ligand for the immune checkpoint receptor PD-1. PD-L2 competes with PD-L1 to bind to PD-1 (expressed by cytotoxic T cells). PD-L2 is expressed by different types of immune cells (antigen-presenting cells such as macrophages and dendritic cells), nonimmune cells and tumour cells Compared to PD-L1, PD-L2 has higher affinity for PD-1 receptor but is expressed at a lower level. Expression of PD-L2 by tumour cells downregulates T cell proliferation and functioning, by binding with PD-1.

Importance

  • PD-L2 is a protein ligand for PD-1.
  • PD-L2 is expressed on immune, non-immune and tumour cells, while PD-1 is expressed on cytotoxic T cells.
  • Compared to PD-L1, PD-L2 has a higher affinity for PD-1, but is expressed at a lower level.
  • Expression of PD-L2 by tumour cells helps to evade immune response by inhibiting T cells proliferation and functioning.

TILs

Tumour infiltrating lymphocytes (TILs) are immune cell population comprising of cytotoxic T cells and natural killer cells that invade the tumour and its microenvironment. Tumour infiltrating lymphocytes is associated with tumour inflammation.

Importance

  • TILs are immune cells comprising of cytotoxic T cells and natural killer cells.
  • TILs infiltrate tumour and its microenvironment to elicit anti-tumour immune response.
  • Expression of chemokines and proinflammatory cytokines within the tumour microenvironment help in recruiting TILs at tumour sites.
  • The extent of TIL invasion correlates with the tumour inflammation.
  • TILs are being evaluated as predictive biomarkers for therapeutic efficacy and outcome.

Inflammation Gene Signatures

Tumour inflammation gene signatures are gene expression profiles (GEPs) that can be used to understand immune cell infiltration and other inflammation signatures of tumour microenvironment. They can be used as powerful diagnostic tool to differentiate different stages of tumour progression and assess immune response.

Importance

  • Inflammation gene signatures, are gene expression profiles (GEPs), reflecting the genes that are expressed during inflammation, and can thus be used to assess tumour inflammation.
  • Inflammation gene signatures can be assessed by mRNA expression profiling and RNA-sequencing.
  • Inflammation gene signatures can be used to evaluate the presence or absence of immune cells in the tumour microenvironment.
  • Inflammation gene signatures can vary across tumour types.
  • Inflammation gene signatures, such as the interferon gamma (IFN-γ) gene signature help to assess systemic autoimmune pathogenesis.
  • Assessing the sustained IFNγ signature can indicate the level of inflammation in the tumour microenvironment.