Research ArticleCancer

Selective inhibition of TGFβ1 activation overcomes primary resistance to checkpoint blockade therapy by altering tumor immune landscape

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Science Translational Medicine  25 Mar 2020:
Vol. 12, Issue 536, eaay8456
DOI: 10.1126/scitranslmed.aay8456

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Cancer immunotherapy, including immune checkpoint blockade, has achieved increasing prominence in recent years. Unfortunately, only a fraction of tumors respond to this treatment. Previous studies have suggested that inhibition of transforming growth factor–β (TGFβ) may help overcome resistance to immune checkpoint blockade, but it proved to be too toxic for clinical use. Martin et al. designed a more specific inhibitor, targeting only one isoform of TGFβ. The authors showed that this isoform, TGFβ1, is the most relevant one to target in tumors, then demonstrated the effectiveness and safety of their inhibitor with immune checkpoint blockade in multiple mouse models of cancer.

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