CD274 and neoplasm: PD‐L1 expression in tumor cells has been reported to be associated with higher response rates; however, patients without PD‐L1 expression also show an ICI response.[65] Other biomarkers include TMB, alteration of DNA damage repair genes, and interferon‐γ associated genes; however, all these biomarkers need additional validation for clinical application.[65] As an immune rheostats, the treatment function of ICIs largely depends on pre‐existing anticancer immune responses.[50] Therefore, the immunosuppressive state of TME can be a major obstacle to ICI efficacy.