Fig. 4.

Biomarker-defined responses to pembrolizumab monotherapy identify targetable resistance biology. (A) Tumours have low TMB and low neoantigenicity and lack a T cell-inflamed TME. (B) Tumours can evade the immune response despite high TMB and high neoantigenicity. (C) Although T cells are present, stromal and/or endothelial factors in the TME, low TMB and low neoantigenicity impede their activity. (D) Tumours have high TMB, high neoantigenicity and a T cell-inflamed TME, typified by activated T cells and other immune cells with cytolytic roles. (From Cristescu R et al., Pan-tumor genomic biomarkers for PD-1 checkpoint blockade-based immunotherapy. Science. 2018 Oct 12;362(6411). pii: eaar3593. doi: 10.1126/science.aar3593. Reprinted with permission from The American Association for the Advancement of Science).