KLF4 and neoplasm: In the context of the tumor microenvironment, tumor-derived SHH executes immunosuppressive and tumor-supporting functions by promoting Krüppel-like factor 4 (KLF4)-mediated polarization of M2 tumor-associated macrophages (TAMs) and upregulation of PD-L1 expression in TAMs (Petty et al., 2019, 2021).