We recently demonstrated that Smad3 is essential for the TME‐mediated cancer progression, which largely improved the cancer host survival rate from 50% to be 100% in an experimental Lewis lung carcinoma model (LLC).[10, 11] Nevertheless, systematic inhibition of Smad3 would affect host T cell immunity,[12, 13] which can be avoided by directly targeting the Smad3 downstream signalling.[14, 15, 16] Of note, TME of LLC (LLC‐TME) is resistant to the PD‐L1 targeted therapy.[17] Our studies have identified the MMT process and tumor growth of lung carcinoma were tightly regulated by Smad3. The gene discussed is SMAD3; the disease is neoplasm.