FIGURE 4 from Immune Cell Abundance and T-cell Receptor Landscapes Suggest New Patient Stratification Strategies in Head and Neck Squamous Cell Carcinoma

TLS signatures and TCR repertoire richness as markers of immune “hot” tumors with improved survival outcomes. A, Expression of TLS-specific signature genes and chemokine signaling appears elevated in the cytotoxic and PC high subgroups. Other individual markers associated with TLSs (28) display similar trends. ****, P P P P P > 0.05). B, Protein staining for CD8+/CD3+ T cells and regulatory T cell markers (FOXP3, GITR) by IHC shows increased levels in the cytotoxic groups. TC, staining at the tumor center; IM, staining at the immune margin. Boxplots compare staining levels between independent samples across the five groups: immune-excluded, n = 32; macrophage rich, n = 61; DC rich, n = 41; PC rich, n = 14; cytotoxic, n = 4. C, The TLS signature score is strongly correlated with the observed richness of the TCR repertoire. A grouping of tumor TME subtypes emerges from these two parameters. The density plots along the scatter plot depict the distribution of TLS signature scores and observed TCR richness, respectively, for every immune category. The upper right corner of the scatter plot, comprising all cytotoxic samples, corresponds to an immune “hot” state with high evidence of TLS and high richness of the TCR repertoire. The bottom left corner of the scatter plot is enriched in samples with excluded/weak immunity. D, Patients with an “immune-excluded” phenotype (as classified in B) present a trend for worse overall survival outcomes, while highly cytotoxic tumors confer a survival advantage.