Skip to main content
. 2021 May 24;8:674558. doi: 10.3389/fmolb.2021.674558

FIGURE 1.

FIGURE 1

Predictive biomarkers for ICB efficacy. Tumour intrinsic factors such as genetic instability and mutational load can increase the production of tumour neoantigens in the TME. Antigen is taken up by APCs in the TME. MHC expression on tumour cells, macrophages and dendritic cells can effect antigen presentation to resident T cells and in local lymph nodes. The presence of upregulated immune checkpoints, such as PD‐1, PD‐L1, CTLA‐4 can result in inhibitory signalling to prevent effective activation and differentiation of immune cell susbsets in the TME and lymph node. Levels of expression of these receptors and their ligands may determine the impact of respective monoclonal antibody treatments on anti‐tumour responses. The balance of T cell subsets and B cells determines the immune suppressed or activated status of the anti‐tumour immune response. Anti‐PD‐1 antibodies act in the tumour microenvironment (TME) by disrupting the negative regulation of anti-tumour immunity mediated by PD-1 and its ligands (PD‐L1 and PD‐L2) expressed on somatic cell types and antigen presenting cells (APCs) respectively. Upon exposure to tumour antigen, tumour infiltrating lymphocytes express PD-1 and release pro-inflammatory cytokines, such as interferon‐ γ, which trigger PD‐L1 expression in cells in the TME. PD‐1/PD‐L1 interaction results in T cell exhaustion and inhibition of the antitumour cytotoxic T cell response. Whilst PD‐L1 antibodies act mainly at the TME, anti‐CTLA‐4 antibodies play a role in the local tumour draining lymph node. CTLA‐4 is expressed on the T cell surface in response to T cell receptor engagement and costimulatory signalling through CD28. The mechanism underlying the immune inhibitory function of CTLA‐4 inhibitors relies mainly on the competition of CTLA‐4 and CD28 in binding to the same ligands―CD80 and CD86. Abbreviations: APC ‐ antigen presenting cell, TME ‐ tumour microenvironment, MHC ‐ major histocompatibility complex, PD ‐ programmed death, CTLA ‐ cytotoxic T lymphocyte associated protein, CD ‐ cluster of differentiation, Treg ‐ T regulatory, TCR ‐ T cell receptor, BCR - B cell receptor.