Immunotherapy has revolutionized the treatment of many cancers, but even for the most sensitive tumor types most patients do not respond to current immunotherapy regimens. One major block to effective anti-tumor immunity is inhibition of the function of effector T cells by active TGFβ in tumors. For this reason, several major pharmaceutical companies have invested substantial resources in developing inhibitors of TGFβ ligands or TGFβ signaling to enhance anti-tumor immunity. However, because TGFβ isoforms (TGFβ1, 2 and 3) play multiple important homeostatic roles, highly effective inhibition of TGFβ function causes severe toxicity, as seen by the embryonic or perinatal lethality of knockout of each of the 3 mammalian TGFβs. Even the relatively ineffective TGFβ inhibitors that have entered clinical trials have been withdrawn because of unacceptable toxicity (cardiac valve thickening and skin cancer). We have thus spent the past 20 years developing drugs targeting TGFβ activating integrins, which only activate a small fraction of extracellular latent TGFβ in precise contexts relevant to specific diseases, with the goal of increasing precision and greatly reducing the potential for toxicity.