The solid stress-induced hypoxia could also induce metabolic rewiring in tumor cells and CAFs toward glycolysis via HIF-1α-mediated reprograming eventually leading to rapid TME acidification, which could induce T cell inhibition via decreasing expression of major TCR components, reduced secretion of IL-2, tumor necrosis factor alpha (TNFα) and interferon-gamma (IFNγ) and upregulated expression of immune checkpoints (89–91). Here, TNF is linked to neoplasm.