Upregulation of lung cancer-intrinsic USP17 (also known as DUB3) induced by TAM-secreted inflammatory stimuli protects interferon regulatory factor 5 (IRF5), c-Rel, and NF-κB-inducing kinase (NIK) from TRAF2/3-mediated ubiquitin‒proteasome degradation, which not only promotes M2 macrophage recruitment to the TME but also forms a positive feedback loop to continuously induce USP17 expression [48] (Fig. 1). Here, USP17L2 is linked to lung cancer.