DKK3 has established roles in modulating various aspects of the TME, such as activation of CAFs and the immune modulation of CD8+ T cells.[17, 38, 39] However, given that DKK3 is just one of many secreted factors in PDAC, the reprogramming of the TME observed in DDKC tumors likely arises not from stromal DKK3 but from the unique intrinsic features and the subsequently altered secretome of DKK3‐knockout cancer cells. Here, DKK3 is linked to cancer.