Figure 2. 4-1BB is a tumor Treg-specific immune checkpoint.

(A) Immune checkpoint expression in peripheral and tumor Tregs. The green dendrogram represents immune checkpoints important for differentiating Treg origin. The top annotation row designates Treg origin and the second annotation row identifies tumor origin. (B) Log₂ fold change of the ratio of tumor to peripheral Treg expression of checkpoint genes. The dashed line represents the median log₂ fold change ratio for all checkpoints. (C) Peripheral and tumor Treg expression of CTLA4, ICOS, TNFRSF4 (OX40), TNFRSF18 (GITR), and TNFRSF9 (4-1BB) expression across 4 cancer types. (D) Representative Z score comparison of CTLA4, ICOS, TNFRSF4, TNFRSF18, and TNFRSF9 expression across 7 cancer types from 4 cancers acquired as a part of this study and 3 published data sets (14, 15). Statistical comparisons were performed using paired t tests to compare peripheral and tumor Tregs for each genes’ expression. Values show in C and D are P values.