5.2.5. Immunocheckpoints (ICs) as Biomarkers

Other important biomarkers being worked with are PD-1 and PD-L1. PD-1 is expressed on most tumour infiltrating T cells, including antigen-specific CD8+ T cells. PD-1 is expressed after T-cell activation and results in the elimination of T cells after they have exerted their function. PD-1 is therefore a checkpoint and serves as a marker for T-cell depletion. Its ligand, PD-L1, is expressed in melanoma tumour cells, non-small cell lung cancer, CRC, bladder cancer, gastric cancer, ovarian cancer, B-cell lymphoma, Merkel cell carcinoma and Hodgkin's lymphoma. If the interaction between PD-1 and its ligand is inhibited by antibodies, the T cells will remain active, mediating antitumour activity [282,312].

Tumour infiltrating immune cells that express PD-1 or PD-L1 are predictive biomarkers for tumours that may respond to T-cell checkpoint blocking. Tumours that have low levels of expression of these molecules have a low response rate to this treatment [282].

Expression of PD-L1 before treatment in tumour cells and immune cells correlates with improved response rates, progression-free survival, and overall survival in pembrilizumab-treated melanoma patients [281].

But the use of PD-1 and PD-L1 still has some drawbacks, such as the expression of PD-L1 is heterogeneous and dynamic within each individual, and even its expression may be induced by activated tumour specific T cells. Its expression may also vary between the primary lesion and its metastasis. In addition, other cell types present in the tumour may express PD-L1, including lymphocytes and macrophages [282,313].
