Fig. 9
Disrupting Blimp1+ Treg activity reshapes the TME for improved tumor control and response to checkpoint blockade. a) Left, Blimp1-sufficient Treg. Treg and TFR cells mainly suppress the cellular and humoral anti-tumor immune responses, respectively. Conversely, tumor cells impose suppression on both cellular and humoral immune responses, but foster the immune suppression by Treg and TFR cells (not depicted). Right, Blimp1-deficient Treg. Deletion of Blimp1 in Treg cells specifically destabilizes and reprograms TIL Treg and TFR cells into Teff, which upregulate Eomes, display impaired suppressive activity and cooperate with both cellular and humoral anti-tumor components to control tumor growth. Disrupting Blimp1+ Treg activity also increases tumor immunogenicity by upregulating MHC-related molecules, reduces IFN-I signature and augments response to checkpoint blockade therapy. MΦ: macrophage. The unclear events are indicated by dashed lines. Not depicted: peripheral TFH and B-cells and their migration into the tumor; expansion of Treg/TFR cells and anti-tumor effector cells; other cells regulating anti-tumor responses (e.g., myeloid-derived suppressor cells, etc.). b) Kaplan-Meier analysis of OS of patient cohorts expressing differential CFP signature (top 33% vs bottom 33%) based on combined log-averaging of CD74, FCER1A and PDCD1 transcript levels from the TCGA-SKCM dataset. P value is generated using two-tailed LogRank test. Median, median survival time