Skip to main content
. Author manuscript; available in PMC: 2016 May 4.
Published in final edited form as: Nat Rev Cancer. 2012 Mar 22;12(4):252–264. doi: 10.1038/nrc3239

Figure 4. Two general mechanisms of expression of immune-checkpoint ligands on tumour cells.

Figure 4

The examples in this figure use the programmed cell death protein 1 (PD1) ligand, PDL1 (also known as B7-H1), for illustrative purposes, although the concept probably applies to multiple immune-checkpoint ligands, including PDL2 (also known as B7-DC). a | Innate immune resistance. In some tumours, constitutive oncogenic signalling can upregulate PDL1 expression on all tumour cells, independently of inflammatory signals in the tumour microenvironment. Activation of the AKT and signal transducer and activator of transcription 3 (STAT3) pathways has been reported to drive PDL1 expression. b | Adaptive immune resistance. In some tumours, PDL1 is not constitutively expressed, but rather it is induced in response to inflammatory signals that are produced by an active antitumour immune response. The non-uniform expression of PDL1, which is commonly restricted to regions of the tumour that have tumour-infiltrating lymphocytes, suggests that PDL1 is adaptively induced as a consequence of immune responses within the tumour microenvironment. Adaptive induction may be a common mechanism for the expression of multiple immune-checkpoint molecules in tumours. IFNγ, interferon-γ; MHC, major histocompatibility complex; TCR, T cell receptor.