Blockade of only TGF-β 1 and 2 is sufficient to enhance the efficacy of vaccine and PD-1 checkpoint blockade immunotherapy

ABSTRACTCheckpoint inhibition has established immunotherapy as a major modality of cancer treatment. However, the success of cancer immunotherapy is still limited as immune regulation of tumor immunity is very complicated and mechanisms involved may also differ among cancer types. Beside checkpoints, other good candidates for immunotherapy are immunosuppressive cytokines. TGF-β is a very potent immunosuppressive cytokine involved in suppression of tumor immunity and also necessary for the function of some regulatory cells. TGF-β has three isoforms, TGF-β 1, 2 and 3. It has been demonstrated in multiple mouse tumor models that inhibition of all three isoforms of TGF-β facilitates natural tumor immunosurveillance and tumor vaccine efficacy. However, individual isoforms of TGF-β are not well studied yet. Here, by using monoclonal antibodies (mAbs) specific for TGF-β isoforms, we asked whether it is necessary to inhibit TGF-β3 to enhance tumor immunity. We found that blockade of TGF-β1 and 2 and of all isofor...