Activation of mesenchymal stem cells by macrophages promotes tumor progression through immune suppressive effects

Abstract

Cancer development and progression is linked to tumor-associated macrophages (TAMs). Distinct TAMs subsets perform either protective or pathogenic effects in cancer. A protective role in carcinogenesis has been described for M1 macrophages, which activate antitumor mechanisms. By comparison, TAMs isolated from solid and metastatic tumors have a suppressive M2-like phenotype, which could support multiple aspects of tumor progression. Currently, it has not been clearly understood how macrophages in tumor-associated stroma could be hijacked to support tumor growth. Mesenchymal stem cells (MSCs) actively interact with components of the innate immune system and display both anti-inflammatory and pro-inflammatory effects. Here, we tested whether MSCs could favor the tumor to escape from immunologic surveillance in the presence of M1 macrophages. We found that MSCs educated by M1 condition medium (cMSCs) possessed a greatly enhanced ability in promoting tumor growth in vivo. Examination of cytokines/chemokines showed that the cMSCs acquired a regulatory profile, which expressed high levels of iNOS and MCP1. Consistent with an elevated MCP1 expression in cMSCs, the tumor-promoting effect of the cMSCs depended on MCP1 mediated macrophage recruitment to tumor sites. Furthermore, IL-6 secreted by the cMSCs could polarize infiltrated TAMs into M2-like macrophages. Therefore, when macrophages changed into M1 pro-inflammation type in tumor microenvironment, the MSCs would act as poor sensors and switchers to accelerate tumor growth.

Tumor-induced neurogenesis and immune evasion as targets of innovative anti-cancer therapies

“…3 In patients, the immune and nervous systems are commonly coopted by tumors to favor cancer progression. [4][5][6] At metastatic stage, the deadliest phase of cancer progression, cancer cells access the systemic circulation, move and implant in distant organs where favorable substrates allow cancer cell colonization and expansion. 7 In the process, reciprocal communication between immune and nervous systems correlates with bad prognosis.…”

“…10 Aberrant characteristics of malignant tissues are further exacerbated by non-transformed cells that join the stroma of growing tumors in response to chemotactic signals. 5 As they multiply in an uncontrolled manner, malignant cells form small tumor masses that require nutrients and oxygen to continue their expansion. 11 Cancer cells at the center of millimetric tumors respond to local hypoxic conditions activating signaling pathways that promote synthesis and release of chemokines and growth factors the transform the local environment.…”

S100A8 facilitates the migration of colorectal cancer cells through regulating macrophages in the inflammatory microenvironment

“…Among the immune cells, macrophages play an indispensable role. For instance, macrophage infiltration in colon tissue has been observed in both inflammatory bowel disease (IBD) and CRC (4), and the cytokines secreted by macrophages under certain conditions have directly or indirectly stimulated inflammation and tumor progression (5,6). Although great progress has been made, the interactions and the molecular mechanisms between CRC and the inflammatory microenvironment remain unknown.…”

Inflammation and cancer interconnection; simply as we think

“…All of these distinct CD4+ T cell types can give a share in tumorigenesis by different paths depending on context. For example, regulatory T immunosuppressive subset of TH cells prevent cytotoxic action of CD8+ T cells through preventing tumor rejection [35]. Although in genericfavoring tumor refuse TH1 cells might contribute to tumor escape through secretion of interferon (IFN)-γ, which triggers expression of apoptosis ligand that provides off signals to cytotoxic T cells.…”