TNF and neoplasm: In this regard, tumor APCs expressing TLRs recognize PVNPs to induce the production of cytokines and chemokines (e.g., IL-1β, IL-6, IL-12p40, MIP1-α, and TNF-α and type I interferon (IFN)) within cold TME and eventually reprogram the suppressed TME to an immune-activated state by converting TME-based TANs and TAMs from a protumor to an antitumor phenotype toward tumor eradication [87] (Figure 3A).