TNF and cancer: In addition, hypoxia induces the expression of cancer-promoting transcription factors such as HIF-1α, which further induces angiogenesis-promoting growth factors such as VEGF and pro-inflammatory cytokines such as TNF-α and IL-1β, as well as the regulation of immune cells, metabolic signaling, and the development of resistance in various types of tumors in the TME (Kumar and Gabrilovich, 2014; Jiang et al., 2020; Roy et al., 2020).