TNF and neoplasm: These results led to the proposal of a novel carcinogenic model, termed the “cold carcinogenic effect.” In this model, the hypothermic environment generated by injury-induced ischemia and hypoxia produces a suitable niche for tumor lesions and then activates adjacent adipocytes to provide the proliferative factors (such as TNF-α and VEGF) and energy-rich nutrients (adipose metabolic products) for malignant progression.