Cancer cell immune escape and tumor progression by exploitation of anti-inflammatory and pro-inflammatory responses.
Apoptotic cells can be eliminated by phagocytosis, which is mediated by antigen-presenting cells (APCs), such as macrophages and dendritic cells (DCs), through phosphatidylserine (PS) on apoptotic cells and phosphatidylserine receptor (PSR) on APCs. The phagocytosis of apoptotic cells by macrophages is strictly regulated by not only the inflammatory reaction, but also by an increase in anti-inflammatory factors such as IL-10, TGF-beta, and prostaglandin E2 (PGE2), leading to an anti-inflammatory situation, whereby apoptosis contributes to a noninflammatory response. However, because PS and PSR are expressed in cancer cells, shed soluble phosphatidylserine (sPS) can interact with the PS receptor on macrophages, which promotes an anti-inflammatory response to macrophages that may lead to immune escape. The sPS derived from cancer cells also reacts with the PSR on the cancer cells to produce IL-10, TGF-beta, and PGE2, which can cause suppression of anti-tumor immunity through the anti-inflammatory response to macrophages, which produces tumor-associated macrophages. Furthermore, sPS and TGF-beta inhibit the maturation of immature DCs, resulting in a functional inhibition of DCs. The potential roles of PS and PSR in cancer cells and macrophages in immune escape mediated by sPS and anti-inflammatory factors are discussed, which may explain their dual regulation of anti- and pro-inflammatory responses during tumor progression.
Kim
Ryungsa
R
International Radiation Information Center, Research Institute for Radiation Biology and Medicine, Hiroshima University, Hiroshima, Japan. rkim@hiroshima-u.ac.jp
Emi
Manabu
M
Tanabe
Kazuaki
K
D017209:Apoptosis / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology*; D018450:Disease Progression; D006801:Humans; D008264:Macrophages / Q000276:immunology*; D018448:Models, Immunological; D009369:Neoplasms / Q000276:immunology* / Q000473:pathology; D010587:Phagocytosis / Q000276:immunology*; D011956:Receptors, Cell Surface / Q000276:immunology* / Q000378:metabolism
D011956:Receptors, Cell Surface; C408123:phosphatidylserine receptor