SMAD4 and neoplasm: The pSMAD2 and 3 form trimeric SMAD complexes with SMAD4, and subsequently regulate downstream genes involved in tumor progression and immunosuppressive microenvironment.30,31 Our findings further supported the mechanism of action of SHR-1701, and suggested that the baseline level of pSMAD2/3 might serve as a predictive biomarker for the efficacy of SHR-1701 plus AG regimen.