These effects have been shown to occur independently of HIF-1α, suggesting the existence of other potential regulatory mechanisms.225 HIF-α activities in CD8+ tumor-infiltrating lymphocytes (TILs) promote their accumulation and anticancer activities,226 as well as the production of interferon-gamma (IFN-γ) by CD4+ T cells.227 HIF-1α deficiency attenuates the ability of some CD8+ T cells to cross the endothelial barrier and reduces the abundance of infiltrating CD8+ T cells in the TME. Here, CD4 is linked to neoplasm.