TGFβ1 neutralization displays therapeutic efficacy through both an immunomodulatory and a non-immune tumor-intrinsic mechanism.

Our results confirm TGFβ1 as the relevant isoform to target for cancer therapy, not only in combination with checkpoint inhibitors, but also with other immunotherapies such as cancer vaccines. Moreover, TGFβ1 blockade can also act as a monotherapy, through a tumor-intrinsic effect blocking the EMT-like transition. Because human melanomas that resist therapy often express a gene signature that links TGFβ1 with EMT-related genes, these results support the clinical development of TGFβ1-specific mAbs in melanoma.