Fig. 3.
Therapeutic strategies against cancer-induced chronic inflammation. Inhibiting tumor cell–intrinsic proinflammatory functions [such as blunting NF-κB/STAT3/phosphatidylinositol 3-kinase (PI3K)–Akt pathways or downstream effectors]. Moreover, turning lymphocytes into effector TH1/TC1 cells necessitates effective reprogramming of type 2 macrophages or immunosuppressive DCs by a concerted action of pattern recognition receptors, the inflammasome platform, or CD40 costimulation, as well as neutralization of immune checkpoint ligand/receptor interaction. In parallel, reducing the accumulation or migration of suppressive myeloid cells in primary sites or distant niches while promoting cytoreduction/debulking with irradiation, cytotoxic compounds, or antiangiogenic molecules may synergistically gear the host/tumor imbalance toward durable tumor regression. HIF-1, hypoxia-inducible factor 1; AMPK, adenosine monophosphate–activated protein kinase; JAK2, Janus kinase 2; CDDO, 2-cyano- 3,12-dioxooleana-1,9(11)-dien-28-oic acid; TLR7, Toll-like receptor 7; COX2, cyclooxygenase; ICD, immunogenic cell death.