Fig. 3: Single-cell TCR sequencing analyses demonstrate conserved clonal and phenotypic architecture of post-radiation repopulating TILs except for the persistent loss of ICRhigh clonotypes, which demonstrate extensive clonal overlap with proliferative TILs suggesting tumor-reactivity.
a Clonal frequency projections onto T cell UMAP profiles from all 11 HyPR-HN datasets demonstrate a diverse T cell landscape of both singletons and hyper-expanded clones. Repopulating T cells largely recapitulate the pre-treatment clonal architecture, particularly among less differentiated states including naïve-like and pre-exhausted populations. b While exhausted CD8 T cell clonotypes have overlap with several sub-clusters, they demonstrate the greatest clonal overlap with proliferative TILs, which are subsequently lost post-radiotherapy and do not return to the tumor microenvironment. c Overlapping exhausted and proliferative TIL clonotypes contain a conserved and unique gene transcriptional profile suggesting tumor antigen-reactivity. Pre-ex Pre-exhausted T cells, Reg Regulatory T cells, TRM Tissue-resident memory T cells, Prolif Proliferative T cells, ExCD8 Exhausted CD8 T cells, ExCD4 Exhausted CD4 T cells, IFN Type I interferon-responsive T cells.
