Table 1 The role of COX-2 as an oncogene or suppression of tumor immunity
From: Cyclooxygenase-2 promotes tumor growth and suppresses tumor immunity
Oncogene | Promotes angiogenesis and tissue invasion of tumors [7, 8], resistance to apoptosis [9, 10] |
COX-2-PGE2-Prostaglandin E Receptors signal pathway [12] | |
PI3K-dependent pathway [16] | |
Extracellular signal-regulated kinases (ERKs) [17] | |
Early growth response factor 1 (EGR-1) [18] | |
Innate immunity | |
Macrophages | Augment pro-tumorigenic type 2 lymphocyte [22] |
Natural Killer (NK) cells | Inhibits the potential of NK cells to migrate, exert cytotoxic effects, and secrete interferonγ [26] |
Inhibits major NK receptors (NKR): NKG2D, CD16 and natural cytotoxicity receptors (NCR: NKp30, NKp44, NKp46) [27] | |
Dendritic cells | A key immunomodulator of DC biology [28] |
Reduces the maturation of DCs and their expression of MHC class II molecules [29] | |
The production of endogenous IL-10 adaptive immunity | |
Adaptive immunity | |
B and T cells | Inhibits proliferation of B and T lymphocytes [31] |
Bluntes the interferon-gamma release of antigen-specific T cells and increased the expression of interleukin-4 and indoleamine | |
2,3-dioxygenase by tumor cells [32] | |
γδ T cells | Inhibits γδ T cell receptors TCR Vγ9Vδ2, NKG2D, CD16 [27] |
Tregs | Induces Tregs [34] |
Promotes CD4+ and CD8+ T cells differentiation in Tregs [33] | |
Inhibits effector T cells in a COX-2-dependent manner [35, 36] | |
MDSC | COX-2 would maintain elevated MDSC levels [40] |