Fig. 7: A proposed model shows that HIS reflects the dynamic features of tumor immune evasion and dictates the selective efficacy of ICB in a tumor size-dependent manner. | Cell Death & Disease

Fig. 7: A proposed model shows that HIS reflects the dynamic features of tumor immune evasion and dictates the selective efficacy of ICB in a tumor size-dependent manner.

From: High baseline levels of PD-L1 reduce the heterogeneity of immune checkpoint signature and sensitize anti-PD1 therapy in lung and colorectal cancers

Fig. 7

During early tumorigenesis, immune checkpoints are usually expressed at relatively low levels (HIS-low), thus sensitive to ICB therapy. Following tumor progression, the TME becomes increasingly immune suppressive to evade host immunosurveillance. This process involves two potential mechanisms: a stochastic upregulation of multiple immune checkpoints, leading to HIS-high and resistance to ICB therapy (Majority), or overexpression of a few pivotal immune checkpoints while maintaining others at lower levels (Minority). Therefore, the elevated expression of key immune checkpoints reduces the HIS in large tumors compared to small tumors, rendering those large tumors sensitive to blocking the predominant immunosuppressive signal in the TME. ICB immune checkpoint blockade, HIS heterogeneity of immune checkpoint signature.

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