In addition, the regulatory networks dependent on TCF4/BRD4, MYC, the cytoprotective enzyme heme oxygenase-1 (HO-1), the loss of Kelch-like ECH-associated protein 1 (KEAP1), and the loss of E-cadherin have been considered resistance-driver factors against immune checkpoint blockades in melanoma patients [63,64,65,66,67]. The gene discussed is TCF4; the disease is melanoma.