Table I. Summary of cancer–immune cell interactions and their functional consequences
Cell TypeIn Primary TumorDuring TransitionAt Metastatic Site
Effects of tumor-infiltrating immune cells on cancer cell EMT
 TAMsRecruited by CCL2 (17, 18)Prevent anoikis (24, 25)Promote metastasis (17)
Secrete TGF-β, PDGF, EGF, TNF-α, IL-1, and IL-6 (11, 17, 18)Tumor cell survival (21, 2325)
Induce EMT (11, 17)Degrade ECM (21, 23)
Promote angiogenesis and tumor growth (11, 16)Aid intra- and extravasation (22, 23)
 MonocytesSecrete TGF-β, PDGF, EGF, TNF-α, IL-1, and IL-6 (11, 17, 21)Aid intra- and extravasation (27)pMOs inhibit metastasis (28)
  Induce EMT?
 NeutrophilsRecruited by CXCL15 and HMGB1 (32)NETs trap cancer cells (30, 31)Promote metastasis (30, 31)
Promote tumor growth?
 MDSCsSecrete MMPs, CXCL5, CXCL12, VEGF, bFGF, HGF, TGF-β (45)Establish premetastatic niche by versican secretion (46)
Induce EMT (44)
Promote tumor growth (4043)
 PlateletsShield from NK cells (38)Promote metastasis (34)
Sustain EMT via TGF-β (36)
Aid in extravasation (37)
 ComplementInduces EMT via C3a → TWIST (48)C3a sustains EMT (48)
Promotes tumor growth (48)
 T cellsPromote tumor growth (51)
Induce EMT via Tregs?
Impact of EMT on immune cell functions
 MacrophagesPromote M1→M2 via IL-4, GM-CSF, TGF-β (27)
M2 via TGF-β–induced IRAK-M (49)
Promote tumor growth (49)
 ComplementInduce CD59 on tumor cells (59)Promote metastasis (59)
Resistance to CDC (59)
 T cellsInduce Tregs (51)Evasion of CTLs (52)Tumor autophagy blocks CTL synapse formation (52)Promote metastasis (51)
 NK cellsSecrete soluble ligands (69)Promote tumor growth?Induce activating ligands [NKG2D ligand (69), nectins (71, 72)]Inhibit metastasis? (68)
Suppress inhibitory ligands (epithelial cadherin) (69)Secreted soluble NKG2D ligand leads to suppression?