Extended Data Fig. 4. Antitumor immunity and immune evasion in SyS.

(a) CD8 T cell clones, stratified based on clone size (x axis) and tumor (color). (b) Overall expression of the T cell expansion program in CD8 T cells with a reconstructed TCR (TCR⁺), when stratified based on clonality (Clone⁺ and Clone⁻, denoting clone size greater or equal to 1, respectively). (c) The cancer testis antigens CTAG1A, CTAG1B (encoding for NY-ESO-1), and PRAME are exclusively expressed by SyS malignant (n = 4,371) cells compared to non-malignant ones (n = 2,375). Log-transformed TPM (y axis) in different cell subsets (x axis); p-values: one-sided Mann-Whitney test. (d) tSNE of macrophage profiles, colored by M1/M2 polarization scores, according to signatures defined here (Supplementary Table 4). (e) M1/M2 polarization scores (y axis) according to previously defined signatures⁴² in macrophages in our datasets partitioned to M1-like and M2-like subgroups (p-value: two-sided t-test). (f) Spearman correlation coefficient (color bar) between each pair of genes from M1 and M2 signatures defined here (top, Supplementary Table 4) or previously⁴² (bottom) across macrophages in SyS (left) and melanoma³⁰ (right). (g) Overall Expression of the immune cell signatures (y axis, Online Methods) in SyS tumors (orange) and other cancer types (green); p-value: one-sided t-test. (c) and (g) middle line: median; box edges: 25^th and 75^th percentiles, whiskers: most extreme points that do not exceed ±IQR*1.5; further outliers are marked individually. (h) Prognostic value of T cell levels in different tumor types. Kaplan-Meier (KM) curves of survival in melanoma (left; TCGA), sarcoma (middle)²¹, and SyS (8) (right), stratified by high (top 25%, red), low (bottom 25%, blue), or intermediate (remainder, green) levels of inferred T cell infiltration levels; P: COX regression. (i) Protein expression (CyCIF) of core oncogenic program markers in immune-enriched and deprived niches.