Fig. 5: Validation of spatial relationship biomarkers of ICI response in an independent cohort of pre-operative ipilimumab+nivolumab in head and neck cancer.

A Scale vs. shape SR parameters fitted on the 1-NN distribution for the 25 samples and the 7 × 7 cell type combinations obtained in the head and neck cancer data (right, IMCISION) and UC data (left, NABUCCO). B Scatter plot of the scale-shape parameter space by neighbor cell type (cell to) obtained in the IMCISION trial data. Cohort averages for their associated spatial parameters are highlighted as big dots for each cell type-cell type combination. C Median first nearest-neighbor distance distribution in head and neck cancer samples per response group (n = 9 independent responders and n = 16 independent non-responders) as calculated by the associated shape and scale for the SRs that significantly (FDR < 0.04) associated with response in UC and statistical significance by a Mann–Whitney test. No adjustments were made for multiple comparisons (adjustments for multiple hypothesis testing were done on the shape and scale parameters space in Supplementary Fig. 11). The box plots in each panel show the middle 50% of the data, with the box itself representing the median and the interquartile range (IQR) between the 25th and 75th percentiles. The whiskers extend from the box to the furthest data points within 1.5 times the IQR from the median. Unless otherwise stated, all statistical tests were two-sided. Icons from (A, B, F, G) were adapted from bioIcons (cancerous-cell-1, lymphocytes-4, macrophage, t-lymphocyte, b-lymphocyte, fibroblast-1 licensed under CC-BY 3.0 Unported by Servier), flaticon.com (bladder icon, https://www.flaticon.com/free-icon/bladder_1453578; head neck icon, https://www.flaticon.com/free-icon/injection_4418017). SR: spatial relationship; ICI: immune checkpoint inhibitors; 1-NN: first nearest neighbor; UC: urothelial cancer. Source data are provided with this paper.