Fig. 8: Post-radiation TIL repopulation is driven primarily by returning high-frequency non-tumor-specific circulating clonotypes and newly infiltrating regulatory and naïve clones.
Integrated single-cell sequencing across treatment timepoints demonstrates extensive clonal overlap between high-frequency circulating clonotypes and the pre-exhausted sub-cluster within tumors, showing that T cell re-infiltration after radiation-induced TIL depletion is driven in part by common circulating clonotypes in both (a, b) HyPR-HN Patient 02 and (c, d) HyPR-HN Patient 04. Clonal mapping of post-radiation regulatory and naïve clonotypes further demonstrates that these sub-clusters are composed largely of new clonotypes not seen in the pre-treatment tumor in both (e) HyPR-HN Patient 02 and (f) HyPR-HN Patient 04. 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.
