Research Paper Volume 14, Issue 10 pp 4586—4605

Construction and validation of an immunoediting-based optimized neoantigen load (ioTNL) model to predict the response and prognosis of immune checkpoint therapy in various cancers

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Figure 1. The model of immunoediting-based optimized neoantigen load (ioTNL). (A) Illustration showing the concept of ioTNL model. Left, due to the instability of the genome, the tumor produces different clones. If tumor clones acquired immune escape and immune tolerance to neoantigens, they would not contribute to the tumor immunogenicity and would be discarded. Only the tumor clones with immune clearance ability would be retained. Right, we demonstrated a hypothetical tumor of three clones. Tumor cells from clone 1 and clone 2 were immune-eliminated cells while tumor cells from clone 3 were immunoedited cells. We assumed that this tumor had five neoantigens so that the tumor neoantigen load was equal to 5. However, neoantigens from immunoedited cells were excluded so that the ioTNL score of this tumor was equal to 1.1. (B) Distribution of ioTNL score in the NSCLC cohort. Patients with objective response (ORR) were labeled in blue while patients with non-objective response (NOR) were labeled in cyan. The scores of ioTNL were transformed into log10 format. (C) Boxplot of the distribution of ioTNL scores between patients with ORR and NOR. (D) Sensitivity and specificity of ioTNL in predicting ORR and DCB in NSCLC cohort. (E) Barplots of ORR rate (left) and DCB rate (right) between ioTNL-H group and ioTNL-L group.