SMAD3 and non-small cell lung carcinoma: Research has shown that anti-PD-1 resistance and immune evasion enhanced by SOX4 in non-small cell lung cancer.[109] Importantly, SOX4 can redirect TGF-β-mediated SMAD3-transcriptional output in a context-dependent manner to promote tumorigenesis.[114] This pathway regulates expression of a number of key immune checkpoint proteins including PD-L1, VISTA, galectin-9[115] as well as indoleamine-2,3-dioxygenase.[116] This cross-linking between SOX4 and TGF-β-Smad3 signaling pathways plays a crucial role in the expression of immune checkpoint proteins.