Analysis of tumor groups. (A) Principal component analysis of 3 microenvironment populations (CD4 TILs, CD8 TILs, and tumor) in clonotypic samples demonstrates the similarity of the TIL populations across patients, as well as the heterogeneity of the tumor populations, which appear to cluster in 3 groups. (B) Heat map of the 3 tumor populations clustered using K-means into 3 groups: evasive, exhausted, and cold. The different phenotypes of these groups can be visualized, particularly in the PD-1, PD-L1, HLA-DR, FasR, and MHC-I parameters. The data are color-coded by fold change expression of surface marker vs PB equivalent subset (red = increase, blue = decrease). (C) Comparison of the 3 clusters’ phenotype, including CD4 and CD8 TILs. (D) tSNE dimension reduction of the representative samples from each subgroup. The “evasive” group is characterized by high PD-L1 tumor expression, compared with high PD-1 expression in the “exhausted” group. The “cold” group is characterized by low HLA-DR on the tumor cells, and the TIM-3⁺ TIL CD8⁺ subset can be seen here. *P < .05; **P < .01. ns, not significant.