Recently, it has been demonstrated that the immunological configuration of TME doesn’t only exhibit some signs of oncogenic pathway-driven immunosuppression (such as PD-L1 upregulation), but also requires stress response pathways to support the establishment of immunological ‘cold’ TME (also as non-oncogene addiction).37 The term non-oncogene addiction means these stress response pathways are unable to drive oncogenesis by themselves, but are required for cancer progression through orchestrating TME. This evidence concerns the gene CD274 and cancer.