TNF and cancer: Recently, however, a pro-tumor M1 macrophage subtype was described in melanoma (23) and characterized by increasing the formation of a dense matrix around cancer cells via upregulating HA synthase 2 (HAS2) due to the activation of the TNFα signaling via NFκB, which in turn, was shown in the current study also to be augmented in HPV-negative OPSCC tumors (Fig. 1A).