Figure 5: TCE-mediated tumor growth control is associated with clonal replacement followed by activation of CD8⁺ TILs.

(A) Bar charts describing the proportions of rare (<0.01%), small (0.01-0.1%), medium (0.1-1%), and large (1-10%) CD8⁺ TIL clone sizes represented in each treatment arm.

(B) Heatmap depicting the phenotypic distribution of individual TCR clones across CD8⁺ TIL subsets (bottom) along with histogram of TCR clone frequency (top). Individual clones are grouped by hierarchical clustering of the clone fraction matrix.

(C) UMAP visualization of CD8⁺ TIL gene expression space for cells with detectable TCRs colored by clone size (left) or subtype (right). CD8⁺ TIL subtypes associated with rare or expanded clones are highlighted with dotted lines.

(D) UMAP visualization of effector, Tex, and Tex-prolif CD8⁺ TIL gene expression space colored by clone size or subtype (left) or by treatment groups (right). CD8⁺ TIL subtypes associated with clonal diversity or bifurcated clonality are highlighted with dotted lines.

(E) Bar charts describing the proportions of rare (<0.01%), small (0.01-0.1%), medium (0.1-1%), and large (1-10%) clone sizes among effector, Tex, and Tex-prolif CD8⁺ TILs.

(F) Z-score heatmap of the average expression of marker genes distinguishing the clonally-expanded and diverse Tex-prolif populations. Genes grouped by hierarchical clustering of the z-score matrix.

(G) Violin plots of a subset of clonally-expanded and diverse Tex-prolif marker genes in the full Tex-prolif population binned by treatment group.

(H) Z-score heatmap of the average expression of glycolysis, effector/co-stimulation, and T cell dysfunction gene markers in clonally diverse CD8⁺ TILs subsetted by therapy group (TCE monotherapy and combination therapy highlighted).

* p < 0.05 Bonferroni-corrected Wilcoxon rank-sum test.