Extended Data Fig. 3: Evolution of sTILs, stromal CD8+ cells, PD-L1 expression and immune-related gene sets from paired primary tumors, local recurrences and metastasis.

(A) Percentage of stromal tumor-infiltrating lymphocytes (sTILs) in paired primary tumors, recurrences, and metastases. N = 43 samples. (B) Percentage of CD8+ T cells in the stromal area (immunohistochemistry). N as in (A). (C) Percentage of patients with clinical benefit and PD-L1 expression (clone SP142) in metastatic lesions. A cut-off of 1% expression on immune cells was used to determine PD-L1 positivity. Statistics by Fisher’s exact test (primary versus metastasis) for proportions. N as in (A). (D) Gene expression of an IFNy signature²⁷. N = 30 samples. (E) Gene expression of an exhausted T-cell signature²⁸. N as in (D). (F) Gene expression of a tertiary lymphoid structure (TLS) signature²⁹. N as in (D). (G) Gene expression of an immune checkpoint signature³⁰. N as in (D). (H) Gene set enrichment score of the HALLMARK Oxidative Phosphorylation gene set. N as in (D). (I) Gene set enrichment score of the HALLMARK Glycolysis gene set. N as in (D). (J) Gene set enrichment score of HALLMARK mTOR signaling gene set. N as in (D). (K) Gene set enrichment score of HALLMARK MYC targets gene set. N as in (D). (A, B), (D–K) Boxplots display a minimum (Q0), a maximum (Q4), a median (Q2) and the interquartile range. Statistics with two-sided Wilcoxon-signed-rank on paired primary tumors and metastasis, the number of patients in each analysis are listed between brackets behind the p-value. Red squares indicate patients with clinical benefit, black dots patients with no clinical benefit. Metastatic lesions correspond with baseline samples presented in Fig. 2, Fig. 4, Extended Data Figs. 2, 4 and 6.