SMAD4 and neoplasm: Recent studies have indicated that SMAD4 deficiency may potentially increase tumor immunogenicity by altering the expression of immune-modulating factors, including cytokines, chemokines, and immune checkpoint molecules like PD-L1, and by altering the release of tumor cell surface antigens, thus impacting the interactions between tumor cells and the host immune system.2,40 Additionally, the inactivation of SMAD4 could lead to an increased state of local immune suppression, further allowing tumor cells to evade surveillance and elimination by the body’s immune system.