Cancer cell immune escape and tumor progression by exploitation of anti-inflammatory and pro-inflammatory responses

Abstract

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-β, and prostaglandin E 2 (PGE 2 ), 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-β, and PGE 2 , which can cause suppression of anti-tumor immunity through the anti-inflammatory response to macrophages, which produces tumor-associated macrophages. Furthermore, sPS and TGF-β 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.

Antisense and nonantisense effects of antisense Bcl-2 on multiple roles of Bcl-2 as a chemosensitizer in cancer therapy

“…53,56,58 This is because the immune cells such as antigen-presenting cells (APCs) are shifted in anti-inflammatory situations by IL-10, transforming growth factor-b and prostaglandin E 2 , which are induced by tumor-associated macrophages and tumorderived soluble factors (TDSFs) in the tumor microenvironment. 62 The immature pDCs are recruited to the tumor site from the bone marrow through stromal-derived factor-1 (SDF-1)/CXCR4 interaction, where they are biochemically and functionally modulated as tumorassociated immature pDCs. This has been attributed to the inhibition of DC and T-cell activation.…”

Cancer immunology and canine malignant melanoma: A comparative review

“…So called "anti-inflammatory" cytokines that suppress anti-tumour immunity such as interleukin-10 (IL-10) and transforming growth factor-β (TGF-β) can be produced by tumour cells and also by regulatory T-cells (Tregs) (Jarnicki et al, 2006;Kim et al, 2005). Decreased antigen presentation and perturbed antigen presenting cell (APC) function also impede the development of protective immunity (Kerkar and Restifo, 2012).…”

A Possible Link Between Autoimmunity and Cancer

“…Although the fact that tumour cells generate pro-inflammatory conditions, the immune cells induce an antiinflammatory environment , due to impaired clearance of apoptotic cells by macrophages during the turnover of tumour cells. The impaired clearance of apoptotic cells induces anti-DNA antibodies to self-antigens that lead to a pseudo-autoimmune status, which, provoking a pro-inflammatory response, allows tumour progression (Kim et al, 2005). The increased concentration of autoantibodies and dendritic cells can induce the production of CD4 + CD25 + regulatory T cells (Tregs) that inhibit T-cell function, causing immunological tolerance (Ward et al, 2004).…”