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. 2023 Jul 18;3(7):1260–1276. doi: 10.1158/2767-9764.CRC-22-0514

FIGURE 4.

FIGURE 4

Identification and validation of RCC-associated TCR motifs. A, Strategy for the identification of RCC-associated motifs. First, GLIPH2 was separately run on the RCC TCRβ-seq samples: tumor (n = 42), healthy kidney (n = 24), and PB (n = 32) samples. The overlap of the motifs is shown on the Venn diagrams. We subsequently pruned the motifs found in other datasets to increase the likeliness of finding RCC-associated motifs. We retained motifs that were only exclusive to or enriched to the tumor, resulting in a total of 7,435 RCC-associated motifs (Supplementary Table S4). RA = Rheumatoid arthritis. B, Validation of RCC-associated TCR motifs. From TCGA cohort (48), we selected samples with at least 100 TCR reads and were left with RCC samples (n = 148), as well as samples from 25 different tumors (n = 1,042). The P value was calculated using the two-sided Wilcoxon test. Tumor sample abbreviations and sample numbers are shown in Supplementary Table S4. Additional validation results are presented in Supplementary Fig. S8. C, Proportion of TCRs with RCC-associated motifs in different tissues (left). TCRs with RCC-associated motifs were calculated in samples from our cohort [patients with RCC sampled from PB (n = 32), healthy kidney (n = 24), tumor (n = 42), pre-REP TIL (n = 7), REP TIL (n = 7), and two comparison cohorts (Emerson and colleagues (46), PB samples (n = 786); Huuhtanen and collegaues (47), melanoma biopsy samples (n = 216)]. The proportion of anti-viral TCRs was also calculated using TCRGP (ref. 32; right). P values were calculated with the Wilcoxon test. Raw data are presented in Supplementary Table S4. D, Stacked barplot showing the proportion of TCRs with RCC-associated motifs and anti-viral TCRs in RCC tumors predicted with TCRGP (32). E, Stacked barplot showing the proportion of TCRs with RCC-associated motifs and TCRGP (32)-predicted anti-viral TCRs in the REP TIL samples. F, The expansion and number of RCC-associated motifs in REP TIL samples. On the left, each colored bar denotes the proportion of individual RCC-associated motifs in each REP TIL sample. The legend for the colors is not shown, as there are 1,790 RCC-associated motifs (please refer to Supplementary Table S4 for all). The right panel shows the total number of different RCC-associated motifs in each REP sample.