Currently, researchers believe that immunotherapy resistance is induced in tumor cells due to the lack of antigenic mutations, altered antigen processing mechanisms, major histocompatibility complex (MHC) dysfunction, human leukocyte antigen (HLA) expression deficiency, β2 microglobulin (β2M) mutations leading to HLA loss, constitutive PD-L1 expression, loss of T cell function, and altered signaling pathways (PI3K, MAPK, WNT, IFN), but it remains unclear about the holistic molecular mechanism leading to the PD-L1 overexpression, and thus, drug resistance under hypoxic conditions [30]. This evidence concerns the gene B2M and neoplasm.