Figure 1.

Intratumoral immune cell state diversity in HNSCC. A, Overview of the analyzed patient cohort. Matched pre- and posttreatment primary tumor biopsies and blood samples [peripheral blood mononuclear cells (PBMC)] were collected from 17 patients (seven NR and 10 RE) who were treated with one cycle of nivolumab (NIVO) and ipilimumab (IPI; week 1), followed by one cycle of nivolumab (week 3) and surgery (week 5). One patient (RE, IMC-04) received two cycles of nivolumab monotherapy, and samples of this patient were left out of all analyses in which response was considered a parameter. Biopsies and blood samples were taken at week 0 and at week 5, at time of surgery. Single-cell RNA and TCR sequencing (10X Genomics) was performed on matched biopsies of all patients. Bulk TCR sequencing was performed on matched blood samples of all responding patients. B, 2D projection of all intratumoral immune cells from all patients, colored by cell state. cDC, conventional dendritic cell; Dysf, dysfunctional; Mono–macro, monocyte–macrophage; pDC, plasmacytoid dendritic cell; Tfh, follicular helper-like T cell. C, Expression of genes that identify the CD4⁺ and CD8⁺ T-cell lineages, NK cells, B cells, and myeloid cells across all metacells, projected on the 2D map shown in B. Color scale bar represents log normalized expression, scaled to the minimum and maximum expression levels for each gene. norm., normalized. D, Heat map of the log normalized unique molecular identifier count of marker genes characterizing different subsets of CD4⁺ and CD8⁺ T cells, NK cells, B cells, and myeloid cells across all patients, grouped and colored by cell state. Color code corresponds to the color code used in B. Color scale bar represents the log normalized expression of the individual genes.