TROP2/claudin program mediates immune exclusion to impede checkpoint blockade in breast cancer

To investigate TROP2-dependent transcriptomic changes in breast cancer, we performed RNA-seq on frozen tumor sections from 4T1 Trop2 wild-type and Trop2 knockout tumors. This dataset was generated to define transcriptional programs regulated by TROP2 in the tumor microenvironment and to determine how TROP2 contributes to immune exclusion and resistance to immune checkpoint blockade. Analysis of these tumors identified TROP2-associated enrichment of cell-cell contact and tight-junction pathways, while inflammatory, antitumor immune response, and T-cell cytotoxicity programs were relatively increased in Trop2 knockout tumors. These findings supported the conclusion that TROP2 promotes a claudin/tight-junction-mediated barrier that limits T-cell infiltration and impairs response to anti-PD-1 therapy in triple-negative breast cancer.