Fig. 5. Neoantigen evolution and neoantigen-T cell interactions.

A UMAP and tSNE of CD8⁺ T cells in lung cancers and melanomas, colored and labeled by 4 main subsets of CD8⁺ lymphocytes. B More fractions of effector/memory cells and progenitor CD8⁺ Tex and less terminally CD8⁺ Tex observed in TCGA tumors with higher NEOITHS (more than median cohort NEOITHS). C The NSCLC and melanoma ICB samples with lower NEOITHS shows increased enrichment of terminally CD8⁺ Tex while higher NEOITHS correlates with activated TILs, effector/memory CD8⁺ T cell and progenitor CD8⁺ Tex. D Expression levels of inhibitory checkpoints negatively correlates with NEOITHS in tumors. E Relapse-free survival and overall survival for NSCLC and melanoma ICB cohorts based on high NEOITHS versus low NEOITHS (mean values of cohort NEOITHS used as cut-off points). F Correlations between TCR repertoire diversity and proportions of CIBERSORTx-inferred CD8⁺ T cells subsets. G Based on NEOITHS and NEO2IS, all included samples were segregated into four subgroups: C1-C4 that correspond to distinct TMEs. H CIBERSORTx-estimated immune cell fractions within the defined immune subtypes. I Three immune subgroups were differentiated by distinct clinical response to ICBs in NSCLCs and melanomas. J Kaplan–Meier plots for relapse-free (left panel) and overall survival (right panel) from ICB cohorts stratified by three defined immune subtypes.